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Onco-V™ clinical studies

Our clinical research team have conducted an independent ingredient review and have compiled several clinical studies with the results to demonstrate the ingredient effectiveness to support and help improve health.

Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer Torkelson CJ, et al. Phase 1 Clinical Trial of Trametes versicolor in Women with Breast Cancer. ISRN Oncology. 2012;2012:251632. doi:10.5402/2012/251632. Introduction. Orally administered preparations from the Trametes versicolor (Tv) mushroom have been hypothesized to improve immune response in women with breast cancer after standard chemotherapy and radiotherapy. Methods. A phase I, two-center, dose escalation study was done to determine the maximum tolerated dose of a Tv preparation when taken daily in divided doses for 6 weeks after recent completion of radiotherapy. Eleven participants were recruited and nine women completed the study. Each cohort was comprised of three participants given one of three doses of Tv (3, 6, or 9 grams). Immune data was collected pre- and postradiation, at 3 on-treatment time points and after a 3-week washout. Results. Nine adverse events were reported (7 mild, 1 moderate, and 1 severe), suggesting that Tv was well tolerated. Immunological results indicated trends in (1) increased lymphocyte counts at 6 and 9 grams/day; (2) increased natural killer cell functional activity at 6 grams/day; (3) dose-related increases in CD8+ T cells and CD19+ B cells , but not CD4+ T cells or CD16+56+ NK cells. Conclusion. These findings show that up to 9 grams/day of a Tv preparation is safe and tolerable in women with breast cancer in the postprimary treatment setting. This Tv preparation may improve immune status in immunocompromised breast cancer patients following standard primary oncologic treatment.



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PDQ Integrative, Alternative, and Complementary Therapies Editorial Board. Medicinal Mushrooms (PDQ®): Patient Version. 2017 Oct 24. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK424937/ Medicinal mushrooms are mushrooms that are used as medicine. They have been used to treat infection for hundreds of years, mostly in Asia. Today, medicinal mushrooms are also used to treat lung diseases and cancer. For more than 30 years, medicinal mushrooms have been approved as an addition to standard cancer treatments in Japan and China. In these countries, mushrooms have been used safely for a long time, either alone or combined with chemotherapy. In Asia, there are more than 100 types of mushrooms used to treat cancer. Some of the more common ones are Ganoderma lucidum (reishi), Trametes versicolor or Coriolus versicolor (turkey tail), Lentinus edodes (shiitake), and Grifola frondosa (maitake). Mushrooms are being studied to find out how they affect the immune system and if they stop or slow the growth of tumors or kill tumor cells. It is thought that certain chemical compounds, such as polysaccharides in turkey tail mushrooms, strengthen the immune system to fight cancer. This PDQ cancer information summary gives an overview of the use of medicinal mushrooms in treating cancer. The following information is given for Trametes versicolor, also called Coriolus versicolor (turkey tail), and Ganoderma lucidum (reishi)



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"Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology Guggenheim AG, Wright KM, Zwickey HL. Immune Modulation From Five Major Mushrooms: Application to Integrative Oncology. Integrative Medicine: A Clinician’s Journal. 2014;13(1):32-44. This review discusses the immunological roles of 5 major mushrooms in oncology: Agaricus blazei, Cordyceps sinensis, Grifola frondosa, Ganoderma lucidum, and Trametes versicolor. These mushrooms were selected based on the body of research performed on mushroom immunology in an oncology model. First, this article focuses on how mushrooms modify cytokines within specific cancer models and on how those cytokines affect the disease process. Second, this article examines the direct effect of mushrooms on cancer. Finally, this article presents an analysis of how mushrooms interact with chemotherapeutic agents, including their effects on its efficacy and on the myelosuppression that results from it. For these 5 mushrooms, an abundance of in vitro evidence exists that elucidates the anticancer immunological mechanisms. Preliminary research in humans is also available and is promising for treatment."



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"Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review. Fritz H, et al. Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review. Integr Cancer Ther. 2015 May;14(3):201-11. doi: 10.1177/1534735415572883. Epub 2015 Mar 17. Review. PubMed PMID: 25784670. Polysaccharide K, also known as PSK or Krestin, is derived from the Coriolus versicolor mushroom and is widely used in Japan as an adjuvant immunotherapy for a variety of cancer including lung cancer. Despite reported benefits, there has been no English language synthesis of PSK for lung cancer. To address this knowledge gap, we conducted a systematic review of PSK for the treatment of lung cancer. PSK may improve immune function, reduce tumor-associated symptoms, and extend survival in lung cancer patients. Larger, more rigorous randomized controlled trials for PSK in lung cancer patients are warranted."



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"The use of mushroom glucans and proteoglycans in cancer treatment. Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev. 2000 Feb;5(1):4-27. Review. PubMed PMID: 10696116. Immunoceuticals can be considered as substances having immunotherapeutic efficacy when taken orally. More than 50 mushroom species have yielded potential immunoceuticals that exhibit anticancer activity in vitro or in animal models and of these, six have been investigated in human cancers. All are non-toxic and very well tolerated. Lentinan and schizophyllan have little oral activity. Active Hexose Correlated Compound (AHCC) is poorly defined but has shown early clinical promise. Maitake D-Fraction has limited proof of clinical efficacy to date, but controlled research is underway. Two proteoglycans from Coriolus versicolor - PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide - have demonstrated the most promise. In Japanese trials since 1970, PSK significantly extended survival at five years or beyond in cancers of the stomach, colon-rectum, esophagus, nasopharynx, and lung (non-small cell types), and in a HLA B40-positive breast cancer subset. PSP was subjected to Phase II and Phase III trials in China. In double-blind trials, PSP significantly extended five-year survival in esophageal cancer. PSP significantly improved quality of life, provided substantial pain relief, and enhanced immune status in 70-97 percent of patients with cancers of the stomach, esophagus, lung, ovary, and cervix. PSK and PSP boosted immune cell production, ameliorated chemotherapy symptoms, and enhanced tumor infiltration by dendritic and cytotoxic T-cells. Their extremely high tolerability, proven benefits to survival and quality of life, and compatibility with chemotherapy and radiation therapy makes them well suited for cancer management regimens."



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"Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Fisher M, Yang LX. Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer Res. 2002 May-Jun;22(3):1737-54. Review. PubMed PMID: 12168863. Polysaccharide-K (polysaccharide-Kureha; PSK), also known as krestin, is a unique protein-bound polysaccharide, which has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. PSK and Polysaccharopeptide (PSP) are both protein-bound polysaccharides which are derived from the CM-101 and COV-1 strains of the fungus Coriolus versicolor by Japanese and Chinese researchers, respectively. Both polysaccharide preparations have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer and has therefore undergone more thorough laboratory, animal and clinical testing. Several randomized clinical trials have demonstrated that PSK has great potential as an adjuvant cancer therapy agent, with positive results seen in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunotherapy or biological response modifier (BRM). BRMs potentially have the ability to improve the ""host versus tumor response,"" thereby increasing the ability of the host to defend itself from tumor progression. The mechanisms of biological response modification by PSK have yet to be clearly and completely elucidated. Some studies suggest that PSK may act to increase leukocyte activation and response through up-regulation of key cytokines. Indeed, natural killer (NK) and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies reveal increased expression of key immune cytokines in response to treatment with PSK. An antimetastatic action of PSK has also been demonstrated and is perhaps attributed to its potential to inhibit metalloproteinases and other enzymes involved in metastatic activity. PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect has been attributed to induction of differentiation cytokines. PSK has further been shown to have antioxidant capacity which may allow it to play a role as a normal tissue chemo- and radio-protector when used in combination with adjuvant or definitive chemotherapy and/or radiotherapy in the treatment of cancer, while it may also enable it to defend the host from oxidative stress. Interestingly, studies have also shown that PSK may actually inhibit carcinogenesis by inhibiting the action of various carcinogens on vulnerable cell lines. This action of PSK may play a role in preventing second primary tumors when an inducing agent, such as tobacco or asbestos, is suspected and may also prevent second malignancies due to the carcinogenic effects of radiotherapy and cytotoxic chemotherapy. Another very important aspect of chemoimmunotherapy, in general is that it may be used on debilitated patients such as those with AIDS and the elderly who might otherwise be denied potentially helpful adjuvant cytotoxic chemotherapy. Further determination of the mechanisms of these anti-cancer, immunostimulating and biological response modifying effects of PSK as well as of other protein-bound polysaccharides is certainly warranted. Indeed, with modern cellular and molecular biology techniques, a better understanding of the specific molecular effects of PSK on tumor cells as well as leukocytes may be determined. Much of the research that has been done on PSK is outlined in this paper and may serve as a foundation toward determining the mechanisms of action of this and other protein-bound polysaccharides in the treatment of cancer. This information may open new doors in the development of novel strategies for the treatment of malignancies using adjuvant immunotherapy in combination with surgery, chemotherapy and/or radiotherapy."



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"Recent developments in mushrooms as anti-cancer therapeutics: a review Patel S, Goyal A. Recent developments in mushrooms as anti-cancer therapeutics: a review. 3 Biotech. 2012;2(1):1-15. doi:10.1007/s13205-011-0036-2. From time immemorial, mushrooms have been valued by humankind as a culinary wonder and folk medicine in Oriental practice. The last decade has witnessed the overwhelming interest of western research fraternity in pharmaceutical potential of mushrooms. The chief medicinal uses of mushrooms discovered so far are as anti-oxidant, anti-diabetic, hypocholesterolemic, anti-tumor, anti-cancer, immunomodulatory, anti-allergic, nephroprotective, and anti-microbial agents. The mushrooms credited with success against cancer belong to the genus Phellinus, Pleurotus, Agaricus, Ganoderma, Clitocybe, Antrodia, Trametes, Cordyceps, Xerocomus, Calvatia, Schizophyllum, Flammulina, Suillus, Inonotus, Inocybe, Funlia, Lactarius, Albatrellus, Russula, and Fomes. The anti-cancer compounds play crucial role as reactive oxygen species inducer, mitotic kinase inhibitor, anti-mitotic, angiogenesis inhibitor, topoisomerase inhibitor, leading to apoptosis, and eventually checking cancer proliferation. The present review updates the recent findings on the pharmacologically active compounds, their anti-tumor potential, and underlying mechanism of biological action in order to raise awareness for further investigations to develop cancer therapeutics from mushrooms. The mounting evidences from various research groups across the globe, regarding anti-tumor application of mushroom extracts unarguably make it a fast-track research area worth mass attention."



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"Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells Jiang J, Sliva D. Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells. Int J Oncol. 2010 Dec;37(6):1529-36. PubMed PMID: 21042722. Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases. Currently mushrooms or their extracts are used globally in the form of dietary supplements. In the present study we have evaluated the anticancer effects of the dietary supplement, MycoPhyto® Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and β-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae. Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231. DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion. The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells. In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer."



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"Tocotrienols fight cancer by targeting multiple cell signaling pathways Kannappan R, Gupta SC, Kim JH, Aggarwal BB. Tocotrienols fight cancer by targeting multiple cell signaling pathways. Genes & Nutrition. 2012;7(1):43-52. doi:10.1007/s12263-011-0220-3. Cancer cells are distinguished by several distinct characteristics, such as self-sufficiency in growth signal, resistance to growth inhibition, limitless replicative potential, evasion of apoptosis, sustained angiogenesis, and tissue invasion and metastasis. Tumor cells acquire these properties due to the dysregulation of multiple genes and associated cell signaling pathways, most of which are linked to inflammation. For that reason, rationally designed drugs that target a single gene product are unlikely to be of use in preventing or treating cancer. Moreover, targeted drugs can cause serious and even life-threatening side effects. Therefore, there is an urgent need for safe and effective promiscuous (multitargeted) drugs. “Mother Nature” produces numerous such compounds that regulate multiple cell signaling pathways, are cost effective, exhibit low toxicity, and are readily available. One among these is tocotrienol, a member of the vitamin E family, which has exhibited anticancer properties. This review summarizes data from in vitro and in vivo studies of the effects of tocotrienol on nuclear factor-κB, signal transducer and activator of transcription (STAT) 3, death receptors, apoptosis, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), hypoxia-inducible factor (HIF) 1, growth factor receptor kinases, and angiogenic pathways.



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"Tocotrienols, the Vitamin E of the 21st Century: It’s Potential Against Cancer and Other Chronic Diseases Aggarwal BB, Sundaram C, Prasad S, Kannappan R. Tocotrienols, the Vitamin E of the 21st Century: It’s Potential Against Cancer and Other Chronic Diseases. Biochemical pharmacology. 2010;80(11):1613-1631. doi:10.1016/j.bcp.2010.07.043. Initially discovered in 1938 as a “fertility factor,” vitamin E now refers to eight different isoforms that belong to two categories, four saturated analogues (α, β, γ, and δ) called tocopherols and four unsaturated analogues referred to as tocotrienols. While the tocopherols have been investigated extensively, little is known about the tocotrienols. Very limited studies suggest that both the molecular and therapeutic targets of the tocotrienols are distinct from those of the tocopherols. For instance, suppression of inflammatory transcription factor NF-κB, which is closely linked to tumorigenesis and inhibition of HMG-CoA reductase, mammalian DNA polymerases and certain protein tyrosine kinases, is unique to the tocotrienols. This review examines in detail the molecular targets of the tocotrienols and their roles in cancer, bone resorption, diabetes, and cardiovascular and neurological diseases at both preclinical and clinical levels. As disappointment with the therapeutic value of the tocopherols grows, the potential of these novel vitamin E analogues awaits further investigation."



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"Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population Luk SU, et al. Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population. Int J Cancer. 2011 May 1;128(9):2182-91. doi: 10.1002/ijc.25546. PubMed PMID: 20617516. Emerging evidence supports that prostate cancer originates from a rare subpopulation of cells, namely prostate cancer stem cells (CSCs). Conventional therapies for prostate cancer are believed to mainly target the majority of differentiated tumor cells but spare CSCs, which may account for the subsequent disease relapse after treatment. Therefore, successful elimination of CSCs may be an effective strategy to achieve complete remission from this disease. Gamma-tocotrienols (γ-T3) is one of the vitamin-E constituents, which have been shown to have anticancer effects against a wide range of human cancers. Recently, we have reported that γ-T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel-induced apoptosis, suggesting that γ-T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that γ-T3 can downregulate the expression of prostate CSC markers (CD133/CD44) in androgen-independent prostate cancer cell lines (PC-3 and DU145), as evident from Western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by γ-T3 treatment. In addition, pretreatment of PC-3 cells with γ-T3 was found to suppress tumor initiation ability of the cells. More importantly, although CD133-enriched PC-3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to γ-T3 treatment as the CD133-depleted population. Our data suggest that γ-T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies."



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A new formulation of Gamma Delta Tocotrienol has superior bioavailability compared to existing Tocotrienol-Rich Fraction in healthy human subjects Meganathan P, et al. A new formulation of Gamma Delta Tocotrienol has superior bioavailability compared to existing Tocotrienol-Rich Fraction in healthy human subjects. Scientific Reports. 2015;5:13550. doi:10.1038/srep13550. Gamma and delta tocotrienols are isomers of Vitamin E with established potency in pre-clinical anti-cancer research. This single-dose, randomized, crossover study aimed to compare the safety and bioavailability of a new formulation of Gamma Delta Tocotrienol (GDT) in comparison with the existing Tocotrienol-rich Fraction (TRF) in terms of gamma and delta isomers in healthy volunteers. Subjects were given either two 300 mg GDT (450 mg γ-T3 and 150 mg δ-T3) capsules or four 200 mg TRF (451.2 mg γ-T3 & 102.72 mg δ-T3) capsules and blood samples were taken at several time points over 24 hours. Plasma tocotrienol concentrations were determined using HPLC method. The 90% CI for gamma and delta tocotrienols for the ratio of log-transformation of GDT/TRF for Cmax and AUC0–∞ (values were anti-logged and expressed as a percentage) were beyond the bioequivalence limits (106.21–195.46, 154.11–195.93 and 52.35–99.66, 74.82–89.44 respectively). The Wilcoxon Signed Rank Test for Tmax did not show any significant difference between GDT and TRF for both isomers (p > 0.05). No adverse events were reported during the entire period of study. GDT was found not bioequivalent to TRF, in terms of AUC and Cmax. Gamma tocotrienol in GDT showed superior bioavailability whilst delta tocotrienol showed less bioavailability compared to TRF.



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"δ and γ tocotrienols suppress human hepatocellular carcinoma cell proliferation via regulation of Ras-Raf-MEK-ERK pathway-associated upstream signaling Burdeos GC, Ito J, Eitsuka T, Nakagawa K, Kimura F, Miyazawa T. δ and γ tocotrienols suppress human hepatocellular carcinoma cell proliferation via regulation of Ras-Raf-MEK-ERK pathway-associated upstream signaling. Food Funct. 2016 Oct 12;7(10):4170-4174. PubMed PMID: 27713963. Tocotrienol (T3) has recently gained increasing interest due to its anti-cancer effect. Here, we investigated the modulating effect of δ and γ T3 on the Ras-Raf-MEK-ERK oncogenic upstream signaling pathway in human hepatocellular carcinoma HepG2 cells. The results indicated that T3 regulated the upstream signaling cascades of this pathway."



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"Tocotrienol and cancer metastasis De Silva L, Chuah LH, Meganathan P, Fu JY. Tocotrienol and cancer metastasis. Biofactors. 2016 Mar-Apr;42(2):149-62. doi: 10.1002/biof.1259. Epub 2016 Mar 7. Review. PubMed PMID: 26948691. Tumor metastasis involves some of the most complex and dynamic processes in cancer, often leading to poor quality of life and inevitable death. The search for therapeutic compounds and treatment strategies to prevent and/or manage metastasis is the ultimate challenge to fight cancer. In the past two decades, research focus on vitamin E has had a shift from saturated tocopherols to unsaturated tocotrienols (T3). Despite sharing structural similarities with tocopherols, T3 strive to gain scientific prominence due to their anti-cancer effects. Recent studies have shed some light on the anti-metastatic properties of T3. In this review, the roles of T3 in each step of the metastatic process are discussed. During the invasion process, signaling pathways that regulate the extracellular matrix and tumor cell motility have been reported to be modulated by T3. Although studies on T3 and tumor cell migration are fairly limited, they were shown to play a vital role in the suppression of angiogenesis. Furthermore, the anti-inflammatory effect of T3 could be highly promising in the regulation of tumor microenvironment, which is crucial in supporting tumor growth in distant organs."



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"Anticancer effects of garlic and garlic-derived compounds for breast cancer control Tsubura A, Lai YC, Kuwata M, Uehara N, Yoshizawa K. Anticancer effects of garlic and garlic-derived compounds for breast cancer control. Anticancer Agents Med Chem. 2011 Mar;11(3):249-53. Review. PubMed PMID: 21269259. Garlic and garlic-derived compounds reduce the development of mammary cancer in animals and suppress the growth of human breast cancer cells in culture. Oil-soluble compounds derived from garlic, such as diallyl disulfide (DADS), are more effective than water-soluble compounds in suppressing breast cancer. Mechanisms of action include the activation of metabolizing enzymes that detoxify carcinogens, the suppression of DNA adduct formation, the inhibition of the production of reactive oxygen species, the regulation of cell-cycle arrest and the induction of apoptosis. Selenium-enriched garlic or organoselenium compounds provide more potent protection against mammary carcinogenesis in rats and greater inhibition of breast cancer cells in culture than natural garlic or the respective organosulfur analogues. DADS synergizes the effect of eicosapentaenoic acid, a breast cancer suppressor, and antagonizes the effect of linoleic acid, a breast cancer enhancer. Moreover, garlic extract reduces the side effects caused by anti-cancer agents. Thus, garlic and garlic-derived compounds are promising candidates for breast cancer control."



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"Can garlic reduce risk of cancer? Rivlin RS. Can garlic reduce risk of cancer? The American Journal of Clinical Nutrition. 2009;89(1):17-18. doi:10.3945/ajcn.2008.27181. In addition to inhibiting primary cancer, allium derivatives from garlic may further inhibit metastatic processes. In an androgen-independent prostate cancer mouse model, the water-soluble allium derivative, S-allyllmercaptocysteine, inhibited metastases to the lung and adrenal gland by 90%."



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"Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population Luk SU, et al. Gamma-tocotrienol as an effective agent in targeting prostate cancer stem cell-like population. Int J Cancer. 2011 May 1;128(9):2182-91. doi: 10.1002/ijc.25546. PubMed PMID: 20617516. Emerging evidence supports that prostate cancer originates from a rare subpopulation of cells, namely prostate cancer stem cells (CSCs). Conventional therapies for prostate cancer are believed to mainly target the majority of differentiated tumor cells but spare CSCs, which may account for the subsequent disease relapse after treatment. Therefore, successful elimination of CSCs may be an effective strategy to achieve complete remission from this disease. Gamma-tocotrienols (γ-T3) is one of the vitamin-E constituents, which have been shown to have anticancer effects against a wide range of human cancers. Recently, we have reported that γ-T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel-induced apoptosis, suggesting that γ-T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that γ-T3 can downregulate the expression of prostate CSC markers (CD133/CD44) in androgen-independent prostate cancer cell lines (PC-3 and DU145), as evident from Western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by γ-T3 treatment. In addition, pretreatment of PC-3 cells with γ-T3 was found to suppress tumor initiation ability of the cells. More importantly, although CD133-enriched PC-3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to γ-T3 treatment as the CD133-depleted population. Our data suggest that γ-T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies."



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"Garlic: a review of potential therapeutic effects Bayan L, Koulivand PH, Gorji A. Garlic: a review of potential therapeutic effects. Avicenna Journal of Phytomedicine. 2014;4(1):1-14. Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases.



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"Garlic and onions: Their cancer prevention properties Nicastro HL, Ross SA, Milner JA. Garlic and onions: Their cancer prevention properties. Cancer prevention research (Philadelphia, Pa). 2015;8(3):181-189. doi:10.1158/1940-6207.CAPR-14-0172. The Allium genus includes garlic, onions, shallots, leeks, and chives. These vegetables are popular in cuisines worldwide and are valued for their potential medicinal properties. Epidemiological studies, while limited in their abilities to assess Allium consumption, indicate some associations of Allium vegetable consumption with decreased risk of cancer, particularly cancers of the gastrointestinal tract. Limited intervention studies have been conducted to support these associations. The majority of supportive evidence on Allium vegetables cancer preventive effects comes from mechanistic studies. These studies highlight potential mechanisms of individual sulfur-containing compounds and of various preparations and extracts of these vegetables, including decreased bioactivation of carcinogens, antimicrobial activities, and redox modification. Allium vegetables and their components have effects at each stage of carcinogenesis and affect many biological processes that modify cancer risk. This review discusses the cancer preventive effects of Allium vegetables, particularly garlic and onions, and their bioactive sulfur compounds and highlights research gaps."



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"Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent Thomson M, Ali M. Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. Curr Cancer Drug Targets. 2003 Feb;3(1):67-81. Review. PubMed PMID: 12570662. Garlic [Allium sativum] is among the oldest of all cultivated plants. It has been used as a medicinal agent for thousands of years. It is a remarkable plant, which has multiple beneficial effects such as antimicrobial, antithrombotic, hypolipidemic, antiarthritic, hypoglycemic and antitumor activity. In this review, we will discuss particularly the largely preclinical use of this agent in the treatment and prevention of cancer. A number of studies have demonstrated the chemopreventive activity of garlic by using different garlic preparations including fresh garlic extract, aged garlic, garlic oil and a number of organosulfur compounds derived from garlic. The chemopreventive activity has been attributed to the presence of organosulfur compounds in garlic. How this is achieved is not fully understood, but several modes of action have been proposed. These include its effect on drug metabolizing enzymes, antioxidant properties and tumor growth inhibition. Most of these studies were carried out in the animal models. Also, recent research has focused on the antimutagenic activity of garlic. Recently, it has been observed that aged garlic extract, but not the fresh garlic extract, exhibited radical scavenging activity. The two major compounds in aged garlic, S-allylcysteine and S-allylmercapto-L-cysteine, had the highest radical scavenging activity. In addition, some organosulfur compounds derived from garlic, including S-allylcysteine, have been found to retard the growth of chemically induced and transplantable tumors in several animal models. Therefore, the consumption of garlic may provide some kind of protection from cancer development."



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"The potential application of Allium sativum (garlic) for the treatment of bladder cancer Lamm DL, Riggs DR. The potential application of Allium sativum (garlic) for the treatment of bladder cancer. Urol Clin North Am. 2000 Feb;27(1):157-62, xi. Review. PubMed PMID: 10696254. Additional studies are needed to identify the active ingredients in Allium Sativum (garlic) that are responsible for the observed antitumor activity and immune stimulation. Garlic seems to detoxify chemical carcinogens and prevent carcinogenesis and can also directly inhibit the growth of cancer cells. Current data suggest that low molecular weight sulfur compounds and protein F4 have immune-stimulation properties. Garlic is reported to stimulate immunity, including macrophage activity, natural killer and killer cells, and LAK cells, and to increase the production of IL-2, TNF, and interferon-gamma. These cytokines are associated with the beneficial Th1 antitumor response, which is characteristic of effective cancer immunotherapies. As is true of BCG, garlic stimulates the proliferation of macrophages and lymphocytes and protects against the suppression of immunity by chemotherapy and ultraviolet radiation. Garlic is clearly not a panacea for cancer, but its broad range of beneficial effects are worthy of serious consideration in clinical trials for the prevention and treatment of cancer."



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"Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer Prasad S, Tyagi AK. Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer. Gastroenterology Research and Practice. 2015;2015:142979. doi:10.1155/2015/142979. Gastrointestinal (GI) cancer, a cancer of different organs of the digestive system, is one of the most common cancers around the world. The incidence and death rate of some of these cancers are very high. Although a large variety of chemotherapeutic agents have been introduced since the last few decades to combat GI cancer, most of them are very expensive and have side effects. Therefore, the compounds derived from natural sources, which are considered to be safe and cost effective, are needed. Ginger (Zingiber officinale) is one of the most widely used natural products consumed as a spice and medicine for treating nausea, dysentery, heartburn, flatulence, diarrhea, loss of appetite, infections, cough, and bronchitis. Experimental studies showed that ginger and its active components including 6-gingerol and 6-shogaol exert anticancer activities against GI cancer. The anticancer activity of ginger is attributed to its ability to modulate several signaling molecules like NF-κB, STAT3, MAPK, PI3K, ERK1/2, Akt, TNF-α, COX-2, cyclin D1, cdk, MMP-9, survivin, cIAP-1, XIAP, Bcl-2, caspases, and other cell growth regulatory proteins. In this review, the evidences for the chemopreventive and chemotherapeutic potential of ginger extract and its active components using in vitro, animal models, and patients have been described."



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"Benefits of whole ginger extract in prostate cancer Karna P, et al. Benefits of whole ginger extract in prostate cancer. The British journal of nutrition. 2012;107(4):473-484. doi:10.1017/S0007114511003308. It is appreciated far and wide that increased and regular consumption of fruits and vegetables is linked with noteworthy anticancer benefits. Extensively consumed as a spice in foods and beverages worldwide, ginger (Zingiber officinale Roscoe) is an excellent source of several bioactive phenolics, including non-volatile pungent compounds such as gingerols, paradols, shogaols and gingerones. Ginger has been known to display anti-inflammatory, antioxidant and antiproliferative activities, indicating its promising role as a chemopreventive agent. Here, we show that whole ginger extract (GE) exerts significant growth-inhibitory and death-inductory effects in a spectrum of prostate cancer cells. Comprehensive studies have confirmed that GE perturbed cell-cycle progression, impaired reproductive capacity, modulated cell-cycle and apoptosis regulatory molecules and induced a caspase-driven, mitochondrially mediated apoptosis in human prostate cancer cells. Remarkably, daily oral feeding of 100 mg/kg body weight of GE inhibited growth and progression of PC-3 xenografts by approximately 56 % in nude mice, as shown by measurements of tumour volume. Tumour tissue from GE-treated mice showed reduced proliferation index and widespread apoptosis compared with controls, as determined by immunoblotting and immunohistochemical methods. Most importantly, GE did not exert any detectable toxicity in normal, rapidly dividing tissues such as gut and bone marrow. To the best of our knowledge, this is the first report to demonstrate the in vitro and in vivo anticancer activity of whole GE for the management of prostate cancer."



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"Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells Rhode J, et al. Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells. BMC Complementary and Alternative Medicine. 2007;7:44. doi:10.1186/1472-6882-7-44. Ginger (Zingiber officinale Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component [6]-gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro."



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"Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities Rahmani AH, shabrmi FMA, Aly SM. Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities. International Journal of Physiology, Pathophysiology and Pharmacology. 2014;6(2):125-136. The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities."



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"Ginger-derived phenolic substances with cancer preventive and therapeutic potential Kundu JK, Na HK, Surh YJ. Ginger-derived phenolic substances with cancer preventive and therapeutic potential. Forum Nutr. 2009;61:182-92. doi: 10.1159/000212750. Epub 2009 Apr 7. Review. PubMed PMID: 19367122. Ginger, the rhizomes of Zingiber officinale Roscoe (Zingiberaceae), has widely been used as a spice and condiment in different societies. Besides its food-additive functions, ginger has a long history of medicinal use for the treatment of a variety of human ailments including common colds, fever, rheumatic disorders, gastrointestinal complications, motion sickness, diabetes, cancer, etc. Ginger contains several nonvolatile pungent principles viz. gingerols, shogaols, paradols and zingerone, which account for many of its health beneficial effects. Studies conducted in cultured cells as well as in experimental animals revealed that these pungent phenolics possess anticarcinogenic properties. This chapter summarizes updated information on chemopreventive and chemotherapeutic effects of ginger-derived phenolic substances and their underlying mechanisms."



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"Red ginseng and cancer treatment Wang C-Z, Anderson S, DU W, He T-C, Yuan C-S. Red ginseng and cancer treatment. Chinese journal of natural medicines. 2016;14(1):7-16. doi:10.3724/SP.J.1009.2016.00007. The ginseng family, including Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (notoginseng), is commonly used herbal medicine. White ginseng is prepared by air-drying after harvest, while red ginseng is prepared by a steaming or heating process. The anticancer activity of red ginseng is significantly increased, due to the production of active anticancer ginsenosides during the steaming treatment, compared with that of white ginseng. Thus far, anticancer studies have been mostly focused on Asian ginseng. In this article, we review the research progress made in the anticancer activities of red Asian ginseng, red American ginseng and red notoginseng. The major anticancer mechanisms of red ginseng compounds include cell cycle arrest, induction of apoptosis/paraptosis, and inhibition of angiogenesis. The structure-function relationship analysis has revealed that the protopanaxadiol group ginsenosides have more potent effects than the protopanaxatriol group. Sugar molecules in ginsenosides inversely impact the antiproliferative potential of these compounds. In addition, ginsenoside stereoselectivity and double bond position also influence the anticancer activity. Future studies should focus on characterizing active red ginseng derivatives as potential anticancer drugs."



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"Anti-breast cancer activity of Fine Black ginseng (Panax ginseng Meyer) and ginsenoside Rg5 Kim S-J, Kim AK. Anti-breast cancer activity of Fine Black ginseng (Panax ginseng Meyer) and ginsenoside Rg5. Journal of Ginseng Research. 2015;39(2):125-134. doi:10.1016/j.jgr.2014.09.003. Background: Black ginseng (Ginseng Radix nigra, BG) refers to the ginseng steamed for nine times and fine roots (hairy roots) of that is called fine black ginseng (FBG). It is known that the content of saponin of FBG is higher than that of BG. Therefore, in this study, we examined antitumor effects against MCF-7 breast cancer cells to target the FBG extract and its main component, ginsenoside Rg5 (Rg5). Methods: Action mechanism was determined by MTT assay, cell cycle assay and western blot analysis. Results: The results from MTT assay showed that MCF-7 cell proliferation was inhibited by Rg5 treatment for 24, 48 and 72 h in a dose-dependent manner. Rg5 at different concentrations (0, 25, 50 and 100 μM), induced cell cycle arrest in G0/G1 phase through regulation of cell cycle-related proteins in MCF-7 cells. As shown in the results from western blot analysis, Rg5 increased expression of p53, p21WAF1/CIP1 and p15INK4B and decreased expression of Cyclin D1, Cyclin E2 and CDK4. Expression of apoptosis–related proteins including Bax, PARP and Cytochrome c was also regulated by Rg5. These results indicate that Rg5 stimulated cell apoptosis and cell cycle arrest at G0/G1 phase via regulation of cell cycle-associated proteins in MCF-7 cells. Conclusion: Rg5 promotes breast cancer cell apoptosis in a multi-path manner with higher potency compared to 20(S)-ginsenoside Rg3 (Rg3) in MCF-7 (HER2−/ER+) and MDA-MB-453 (HER2+/ER−) human breast cancer cell lines, and this suggests that Rg5 might be an effective natural new material in improving breast cancer."



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"Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review Chen S, et al. Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review. Evidence-based Complementary and Alternative Medicine : eCAM. 2014;2014:168940. doi:10.1155/2014/168940. Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer."



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"Panax ginseng: a role in cancer therapy? Chang YS, Seo EK, Gyllenhaal C, Block KI. Panax ginseng: a role in cancer therapy? Integr Cancer Ther. 2003 Mar;2(1):13-33. Review. PubMed PMID: 12941165. Panax ginseng is a plant that has been used in traditional medicine in China for thousands of years. It is used as a general tonic or adaptogen with chronically ill patients and is frequently featured in traditional medicine prescriptions from China, Japan, and Korea used by cancer patients. The putative active compounds are the ginsenosides, of which there are more than two dozen. These compounds are found in both Panax ginseng and in other Panax species that are used in herbal medicine. Analysis of ginsenosides is being used in developing quality control assessments for ginseng, which has frequently been adulterated due to its high cost; many currently available standardized extracts do appear to contain the amounts of ginsenosides listed on package labeling. The toxicity of ginseng appears to be low: some of the reports of toxic episodes of ginseng may actually pertain to other components of multicomponent preparations. Very low incidence of toxicity has been observed in ginseng clinical trials using well-characterized preparations. Numerous pharmacological activities of ginseng and the ginsenosides have been explored: the authors review here the activities relating to cancer. Immune system modulation, antistress activities, and antihyperglycemic activities are among the most notable features of ginseng noted in laboratory and clinical analyses. Much testing has been done in humans to explore ginseng's purported antifatigue properties, but this area remains controversial. A number of investigations point to antitumor properties and other pharmacological activities related to cancer, but no trials have yet confirmed a clinically significant anticancer activity. Cancer patients may empirically find ginseng to be useful when they are fatigued, although clinical trials should be conducted to confirm its benefits."



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"Inflammation, cancer, and targets of ginseng Hofseth LJ, Wargovich MJ. Inflammation, cancer, and targets of ginseng. J Nutr. 2007 Jan;137(1 Suppl):183S-185S. Review. PubMed PMID: 17182823. There is evidence that ginseng has potent effects on key players in the inflammatory cascade. For example, ginsan, a polysaccharide extracted from P. ginseng, showed inhibition of s, the p38 MAP kinase pathway, and NF-κB in vitro and inhibition of proinflammatory cytokines in vivo. The ginsenoside Rg3 was shown to inhibit phorbol ester–induced COX-2 and NF-κB induction. BST204, a fermented ginseng extract, can inhibit inducible NOS (iNOS) expression and subsequent nitric oxide production from lipopolysaccharide-stimulated RAW264.7 murine macrophages. In contrast, others showed that incubation of the same cells with P. ginseng showed a dose-dependent stimulation of iNOS. We are currently examining the effects of P. quinquefolius on nitric oxide production in both ANA-1 mouse macrophages and colon cells as a part of ongoing investigations into the potential for ginseng to inhibit colon cancer. We recently showed that P. ginseng can inhibit chemically induced abberant crypt foci in mice. As mentioned, a cytokine storm is associated with active inflammation. It is therefore interesting to find that ginseng inhibits the lipopolysaccharide-induced production of tumor necrosis factor-α and other proinflammatory cytokines by cultured macrophages. Such an effect, therefore, may have a chemopreventive outcome."



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"Enhanced anticancer effects of a mixture of low-dose mushrooms and Panax ginseng root extracts in human colorectal cancer cells Lee MS, et al. Enhanced anticancer effects of a mixture of low-dose mushrooms and Panax ginseng root extracts in human colorectal cancer cells. Oncol Rep. 2017 Sep;38(3):1597-1604. doi: 10.3892/or.2017.5796. Epub 2017 Jul 7. PubMed PMID: 28714027. Worldwide, colorectal cancer is the third most common cancer in men and the second most common in women. As conventional colorectal cancer therapies result in various side effects, there is a need for adjuvant therapy that can enhance the conventional therapies without complications. In this study, we investigated the anticancer effects of combined mixture of the several medicinal mushrooms and Panax ginseng root extracts (also called Amex7) as an adjuvant compound in the treatment of human colorectal cancer. We observed the in vivo inhibitory effect of Amex7 (1.25, 6.25, and 12.5 ml/kg, oral administration, twice daily) on tumor growth in a mouse model xenografted with HT-29 human colorectal cancer cells. In vitro, at 6, 12, and 24 h after 4% Amex7 treatment, we analyzed cell cycle by flow cytometry and the expression levels of cell cycle progression, apoptosis, and DNA damage repair-related proteins using immunoblotting and immunofluorescence staining in HT-29 cell line. As a result, Amex7 significantly suppressed tumor growth in HT-29 human colorectal cancer cells and xenografts. In vitro, Amex7 induced G2/M arrest through the regulation of cell cycle proteins and cell death by apoptosis and autophagy. Additionally, Amex7 consistently induced DNA damage and delayed the repair of Amex7-induced DNA damage by reducing the level of HR repair proteins. In conclusion, Amex7 enhanced anticancer effects through the induction of G2/M arrest and cell death, including apoptosis and autophagy. Furthermore, Amex7 impaired DNA damage repair. The present study provides a scientific rationale for the clinical use of a combined mixture of medicinal mushrooms and P. ginseng root extracts as an adjuvant treatment in human colorectal cancer."



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"Ginseng and cancer Unlu A, Nayir E, Kirca O, Ay H, Ozdogan M. Ginseng and cancer. J BUON. 2016 Nov-Dec;21(6):1383-1387. Review. PubMed PMID: 28039696. Derived from the Greek word Panacea that means 'cure for all', Ginseng (Panax) has had an important place in Chinese Medicine for many of years. As the name suggests, it is believed to be a miraculous plant effective in the treatment of many health problems. It is claimed to have many effects such as sedative, hypnotic, aphrodisiac, antidepressant, diuretic, and stimulating effects, and to be effective in the treatment of certain health problems such as diabetes, Alzheimer's disease, erectile dysfunction and infections. In addition, its effects on the prevention and treatment of cancer as well as on the reduction of cancer-related symptoms have been prioritized in recent years. However, the studies that have been done so far do not confirm these effects. Although certain favorable results have been obtained in some studies intended for investigating its effects on acute nasopharyngitis, diabetes, Alzheimer's disease, and erectile dysfunction, it is early to say anything conclusive. And in cancer patients, it has been shown to be effective in reducing weakness due to cancer and its treatment. On the other hand, ginseng may cause important drug interactions, although it is described as a relatively safe product. For now, it seems to be reasonable to use ginseng only for cancer-related weakness in cancer patients at this point. But this should definitely be done within the knowledge and under the control of oncologists."



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"Cancer and metastasis: prevention and treatment by green tea Khan N, Mukhtar H. Cancer and metastasis: prevention and treatment by green tea. Cancer metastasis reviews. 2010;29(3):435-445. doi:10.1007/s10555-010-9236-1. Metastasis is the most deadly aspect of cancer and results from several interconnected processes including cell proliferation, angiogenesis, cell adhesion, migration, and invasion into the surrounding tissue. The appearance of metastases in organs distant from the primary tumor is the most destructive feature of cancer. Metastasis remains the principal cause of the deaths of cancer patients despite decades of research aimed at restricting tumor growth. Therefore, inhibition of metastasis is one of the most important issues in cancer research. Several in vitro, in vivo, and epidemiological studies have reported that the consumption of green tea may decrease cancer risk. (−)-Epigallocatechin-3-gallate, major component of green tea, has been shown to inhibit tumor invasion and angiogenesis which are essential for tumor growth and metastasis. This article summarizes the effect of green tea and its major polyphenolic compounds on cancer and metastasis against most commonly diagnosed cancer sites."



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"Green tea compounds in breast cancer prevention and treatment Li M-J, Yin Y-C, Wang J, Jiang Y-F. Green tea compounds in breast cancer prevention and treatment. World Journal of Clinical Oncology. 2014;5(3):520-528. doi:10.5306/wjco.v5.i3.520. Breast cancer is the most common cancer among women. In recent years, many in vitro and in vivo studies indicate that green tea possesses anti-cancer effects. The epidemiological studies, however, have produced inconclusive results in humans. Likewise, results from animal models about the preventive or therapeutic effects of green tea components are inconclusive. The mechanisms by which green tea intake may influence the risk of breast cancer in humans remain elusive mechanisms by which green tea intake may influence. Here, we review recent studies of green tea polyphenols and their applications in the prevention and treatment of breast cancer. Furthermore, we discuss the effect of green tea components on breast cancer by reviewing epidemiological studies, animal model studies and clinical trials. At last, we discuss the mechanisms by which green tea components suppress the development and recurrence of breast cancer. A better understanding of the mechanisms will improve the utilization of green tea in breast cancer prevention and therapy and pave the way to novel prevention and treatment strategies for breast cancer."



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"Green tea: Health benefits as cancer preventive for humans Fujiki H. Green tea: Health benefits as cancer preventive for humans. Chem Rec. 2005;5(3):119-32. Review. PubMed PMID: 15889414. Green tea is an acknowledged cancer preventive in Japan. The aim of this review article is to develop the concept of cancer prevention with green tea beverage for humans, which has largely been our exclusive research territory. This paper briefly reviews several topics, beginning with the introduction of our initial work on penta-O-galloyl-beta-D-glucose and (-)-epigallocatechin gallate (EGCG), the main constituent of green tea extract. The mechanisms of EGCG action, particularly the reduction of TNF-alpha are discussed, and we show how use of 3H-EGCG revealed a wide range of target organs for cancer prevention. The results of an epidemiological study in Saitama Prefecture allowed us to determine the cancer preventive amount of green tea-10 Japanese-size cups per day, about 2.5 g green tea extract-which made it possible for us to introduce the two-stage strategy of cancer prevention with green tea. The first stage is the delay of cancer onset for the general population. The second stage is the prevention of recurrence of cancer for patients following cancer treatment. Combination cancer prevention with green tea and cancer preventive drugs is proving especially beneficial for Japanese, who drink green tea every day. And finally, the stimulating comments of Prof. Jim Watson have encouraged green tea scientists."



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"Implications of Green Tea and Its Constituents in the Prevention of Cancer via the Modulation of Cell Signalling Pathway Rahmani AH, Al shabrmi Fahad M., Allemailem KS, Aly SM, Khan MA. Implications of Green Tea and Its Constituents in the Prevention of Cancer via the Modulation of Cell Signalling Pathway. BioMed Research International. 2015;2015:925640. doi:10.1155/2015/925640. Green tea is commonly used as a beverage worldwide, especially in China, Japan, Morocco, and Saudi Arabia. Green tea and its constituents have been considered very effective in the prevention and treatment of various diseases. It contains a variety of catechins, which show a pivotal role in the modulation of biological activities and also act as chemopreventive agents. Earlier studies have confirmed that green tea and its chief constituent epigallocatechin gallate (EGCG) have a potential role in the management of cancer through the modulation of cell signaling pathways. In this review, we focused on the beneficial effects of green tea and its constituents in the cancer prevention and treatment and its impact on modulation of molecular pathways."



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"EGCG, GREEN TEA POLYPHENOLS AND THEIR SYNTHETIC ANALOGS AND PRODRUGS FOR HUMAN CANCER PREVENTION AND TREATMENT Chen D, et al. EGCG, GREEN TEA POLYPHENOLS AND THEIR SYNTHETIC ANALOGS AND PRODRUGS FOR HUMAN CANCER PREVENTION AND TREATMENT. Advances in Clinical Chemistry. 2011;53:155-177. Cancer-preventive effects of tea polyphenols, especially epigallocatechin-3-gallate (EGCG), have been demonstrated by epidemiological, preclinical, and clinical studies. Green tea polyphenols such as EGCG have the potential to affect multiple biological pathways, including gene expression, growth factor-mediated pathways, the mitogen-activated protein kinase-dependent pathway, and the ubiquitin/proteasome degradation pathway. Therefore, identification of the molecular targets of EGCG should greatly facilitate a better understanding of the mechanisms underlying its anticancer and cancer-preventive activities. Performing structure–activity relationship (SAR) studies could also greatly enhance the discovery of novel tea polyphenol analogs as potential anticancer and cancer-preventive agents. In this chapter, we review the relevant literature as it relates to the effects of natural and synthetic green tea polyphenols and EGCG analogs on human cancer cells and their potential molecular targets as well as their antitumor effects. We also discuss the implications of green tea polyphenols in cancer prevention."


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"Biological Effects of Green Tea Capsule Supplementation in Pre-Surgery Postmenopausal Breast Cancer Patients Yu SS, et al. Biological Effects of Green Tea Capsule Supplementation in Pre-Surgery Postmenopausal Breast Cancer Patients. Frontiers in Oncology. 2013;3:298. doi:10.3389/fonc.2013.00298. Regular green tea intake has been associated with an inverse risk of breast cancer. There are compelling experimental evidence that green tea, particularly, epigallocatechin gallate, the most potent green tea catechin, possesses a range of anti-cancer properties. We conducted a pre-surgical study of green tea capsules vs. no-green tea in women with primary breast cancer to determine the effects of green tea supplementation on markers of biological response. Postmenopausal women with ductal carcinoma in situ(DCIS) or stage I or II breast cancer took green tea capsules (940 mg per day) for an average of 35 days prior to surgery (n = 13) or received no green tea (n = 18). Paired diagnostic core biopsy and surgical specimen samples were analyzed for cell proliferation (Ki-67), apoptosis (caspase-3), and angiogenesis (CD34) separately in benign and malignant cell components. There were no significant changes in caspase-3 and CD34 in the green tea and no green tea groups and there were no significant differences in the change in these markers between the two groups. However, Ki-67 levels declined in both benign and malignant cell components in the green tea group; the decline in Ki-67 positivity in malignant cells was not statistically significant (P = 0.10) but was statistically significant in benign cells (P = 0.007). Ki-67 levels in benign and malignant cells did not change significantly in the no green tea group. There was a statistically significant difference in the change in Ki-67 in benign cells (P = 0.033) between the green tea and the no green tea groups. The trend of a consistent reduction in Ki-67 in both benign and malignant cells in the green tea group warrants further investigations in a larger study of breast cancer patients or high-risk women."



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"Both Phenolic and Non-phenolic Green Tea Fractions Inhibit Migration of Cancer Cells Seo EJ, et al. Both Phenolic and Non-phenolic Green Tea Fractions Inhibit Migration of Cancer Cells. Front Pharmacol. 2016 Nov 3;7:398. doi: 10.3389/fphar.2016.00398. eCollection 2016. PubMed PMID: 28194107; PubMed Central PMCID: PMC5278262. Green tea consumption is associated with chemoprevention of many cancer types. Fresh tea leaves are rich in polyphenolic catechins, which can constitute up to 30% of the dry leaf weight. While the polyphenols of green tea have been well investigated, it is still largely unknown, whether or not non-phenolic constituents also reveal chemopreventive and anti-metastatic effects. In this study, we investigated the effects of a fraction of green tea rich in phenolic compounds (PF), a non-phenolic fraction (NPF), which contains glyceroglycolipids (GGL), and a pure glyceroglycolipid compound isolated from the non-phenolic fraction in human cancer. Dried green tea leaves were extracted and applied to a Sephadex LH-20 column. The resazurin reduction assay was used to investigate the cytotoxicity of green tea samples toward human HepG2 hepatocellular carcinoma and normal AML12 hepatocytes cells. Gene expression profiling was performed by mRNA microarray hybridization and the microarray results were validated by RT-PCR. The scratch migration assay was used to investigate the effects of green tea samples on cell migration in vitro. The changes of microtubule dynamics were observed using fluorescence microscopy. PF and NPF were prepared from methanol extract of green tea. A GGL was isolated from NPF. All three green tea samples did not show significant cytotoxic activity up to 10 μg/mL in both HepG2 and AML12 cells, whereas cytotoxicity of the control drug doxorubicin was observed with both cell lines (IC50 on AML12: 0.024 μg/mL, IC50 on HepG2: 2.103 μg/mL). We identified three sets of genes differentially expressed upon treatment with the green tea samples. The genes were associated with cytoskeleton formation, cellular movement, and morphology. The correlation coefficients between mRNA expression values determined by microarray and RT-PCR were R = 0.94. HepG2 and U2OS cells treated with green tea extracts showed the delayed closures. Besides, the number of distinct tubulin filaments decreased upon treatment with green tea samples. We identified not only PF, but also glyceroglycolipids in NPF as contributing factors to the chemopreventive effects of green tea. Both PF and NPF of green tea inhibited cancer cell migration by the disassembly of microtubules, even though they were not cytotoxic."



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"Chemoprevention of oral cancer by green tea Hsu SD, et al. Chemoprevention of oral cancer by green tea. Gen Dent. 2002 Mar-Apr;50(2):140-6. PubMed PMID: 12004708. Green tea has been a popular beverage for many centuries. Only recently, however, has the anti-cancer power of green tea constituents been unveiled. Green tea polyphenols are found to induce apoptosis (programmed cell death) in many types of tumor cells, including oral cancer cells. However, mechanisms that enable normal cells to evade the apoptotic effect still are not understood. In this study, cell growth and invasion assays combined with apoptosis assays were used to examine the effects of green tea extracts, green tea polyphenols, and the most potent green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on normal human keratinocytes and oral carcinoma cells. The results showed that green tea and its constituents selectively induce apoptosis only in oral carcinoma cells, while EGCG was able to inhibit the growth and invasion of oral carcinoma cells. These differential responses to green tea and its constituents between normal and malignant cells were correlated with the induction of p57, a cell cycle regulator. These data suggest that the chemopreventive effects of green tea polyphenols may involve a p57 mediated survival pathway in normal epithelial cells, while oral carcinoma cells undergo an apoptotic pathway. Therefore, regular consumption of green tea could be beneficial in the prevention of oral cancer."



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"Molecular targets for green tea in prostate cancer prevention Adhami VM, Ahmad N, Mukhtar H. Molecular targets for green tea in prostate cancer prevention. J Nutr. 2003 Jul;133(7 Suppl):2417S-2424S. Review. PubMed PMID: 12840218. Prostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer-related deaths in American males. For these reasons, it is necessary to intensify our efforts for better understanding and development of novel treatment and chemopreventive approaches for this disease. In recent years, green tea has gained considerable attention as an agent that could reduce the risk of several cancer types. The cancer-chemopreventive effects of green tea appear to be mediated by the polyphenolic constituents present therein. Based on geographical observations that suggest that the incidence of PCa is lower in Japanese and Chinese populations that consume green tea on a regular basis, we hypothesized that green tea and/or its constituents could be effective for chemoprevention of PCa. To investigate this hypothesis, we initiated a program for the chemoprevention of PCa by green tea. In cell-culture systems that employ human PCa cells DU145 (androgen insensitive) and LNCaP (androgen sensitive), we found that the major polyphenolic constituent (-)-epigallocatechin-3-gallate (EGCG) of green tea induces 1) apoptosis, 2) cell-growth inhibition, and 3) cyclin kinase inhibitor WAF-1/p21-mediated cell-cycle dysregulation. More recently, using a cDNA microarray, we found that EGCG treatment of LNCaP cells results in 1) induction of genes that functionally exhibit growth-inhibitory effects, and 2) repression of genes that belong to the G-protein signaling network. In animal studies that employ a transgenic adenocarcinoma of the mouse prostate (TRAMP), which is a model that mimics progressive forms of human prostatic disease, we observed that oral infusion of a polyphenolic fraction isolated from green tea (GTP) at a human achievable dose (equivalent to 6 cups of green tea/d) significantly inhibits PCa development and metastasis. We extended these studies and more recently observed increased expression of genes related to angiogenesis such as vascular endothelial growth factor (VEGF) and those related to metastasis such as matrix metalloproteinases (MMP)-2 and MMP-9 in prostate cancer of TRAMP mice. Oral feeding of GTP as the sole source of drinking fluid to TRAMP mice results in significant inhibition of VEGF, MMP-2 and MMP-9. These data suggest that there are multiple targets for PCa chemoprevention by green tea and highlight the need for further studies to identify novel pathways that may be modulated by green tea or its polyphenolic constituents that could be further exploited for prevention and/or treatment of PCa."



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"Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics? Brito AF, et al. Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics? Curr Med Chem. 2015;22(26):3025-39. Review. PubMed PMID: 26264923. Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin."



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"Effects of low dose quercetin: Cancer cell-specific inhibition of cell cycle progression Jeong J-H, An JY, Kwon YT, Rhee JG, Lee YJ. Effects of low dose quercetin: Cancer cell-specific inhibition of cell cycle progression. Journal of cellular biochemistry. 2009;106(1):73-82. doi:10.1002/jcb.21977. Quercetin is a flavonoid present in many vegetables, fruits and beverages. Due to its anti-oxidant, anti-tumor and anti-inflammatory activity, quercetin has been studied extensively as a chemoprevention agent in several cancer models. Since most of these studies used higher doses of quercetin than clinically achievable, we focused on the effectiveness of physiologically relevant doses of quercetin. A low dose of quercetin exerted cancer cell-specific inhibition of proliferation and this inhibition resulted from cell cycle arrest at the G1 phase. Quercetin induced p21 CDK inhibitor with a concomitant decrease of phosphorylation of pRb, which inhibits the G1/S cell cycle progression by trapping E2F1. A low dose of quercetin induced mild DNA damage and Chk2 activation, which is the main regulator of p21 expression by quercetin. In addition, quercetin down-regulated the cyclin B1 and CDK1, essential components of G2/M cell cycle progression. Inhibition of the recruitment of key transcription factor NF-Y to cyclin B1 gene promoter by quercetin led to transcriptional inhibition. This study proved that the chemopreventive efficacy of a physiologically relevant dose of quercetin can be achievable through the inhibition of cell cycle progression."



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"Quercetin and Cancer Chemoprevention Gibellini L, Pinti M, Nasi M, et al. Quercetin and Cancer Chemoprevention. Evidence-based Complementary and Alternative Medicine : eCAM. 2011;2011:591356. doi:10.1093/ecam/neq053. Several molecules present in the diet, including flavonoids, can inhibit the growth of cancer cells with an ability to act as “chemopreventers”. Their cancer-preventive effects have been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. The antioxidant activity of chemopreventers has recently received a great interest, essentially because oxidative stress participates in the initiation and progression of different pathological conditions, including cancer. Since antioxidants are capable of preventing oxidative damage, the wide use of natural food-derived antioxidants is receiving greater attention as potential anti-carcinogens. Among flavonoids, quercetin (Qu) is considered an excellent free-radical scavenging antioxidant, even if such an activity strongly depends on the intracellular availability of reduced glutathione. Apart from antioxidant activity, Qu also exerts a direct, pro-apoptotic effect in tumor cells, and can indeed block the growth of several human cancer cell lines at different phases of the cell cycle. Both these effects have been documented in a wide variety of cellular models as well as in animal models. The high toxicity exerted by Qu on cancer cells perfectly matches with the almost total absence of any damages for normal, non-transformed cells. In this review we discuss the molecular mechanisms that are based on the biological effects of Qu, and their relevance for human health."



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"Quercetin suppresses lung cancer growth by targeting Aurora B kinase Xingyu Z, et al. Quercetin suppresses lung cancer growth by targeting Aurora B kinase. Cancer Medicine. 2016;5(11):3156-3165. doi:10.1002/cam4.891. aurora B kinase is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug to treat tumors. Quercetin was identified to be an antitumor agent. Herein, we report for the first time that quercetin inhibited aurora B activities by directly binding with aurora B in vitro and in vivo. Ex vivo studies showed that quercetin inhibited aurora B activities in JB6 Cl41 cells and A549 lung cancer cells. Moreover, knockdown of aurora B in A549 cells decreased their sensitivities to quercetin. In vivo study demonstrated that injection of quercetin in A549 tumor‐bearing mice effectively suppressed cancer growth. The phosphorylation of histone 3 in tumor tissues was also decreased after quercetin treatment. In short, quercetin can suppress growth of lung cancer cells as an aurora B inhibitor both in vitro and in vivo."



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"The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo Angst E, et al. The flavonoid quercetin inhibits pancreatic cancer growth in vitro and in vivo. Pancreas. 2013;42(2):223-229. doi:10.1097/MPA.0b013e318264ccae. The flavonoid quercetin holds promise as an anti-tumor agent in several preclinical animal models. However, the efficacy of oral administration of quercetin in a pancreatic cancer mouse model is unknown. The anti-proliferative effects of quercetin alone or in combination with gemcitabine were tested in two human pancreatic cancer cell lines using cell count and MTT assays. Apoptosis was evaluated by flow cytometry. Tumor growth in vivo was investigated in an orthotopic pancreatic cancer animal model using bioluminescence. Quercetin was administered orally in the diet. Quercetin inhibited the growth of pancreatic cancer cell lines, which was caused by an induction of apoptosis. In addition, dietary supplementation of quercetin attenuated the growth of orthotopically transplanted pancreatic xenografts. The combination of gemcitabine and quercetin had no additional effect compared to quercetin alone. In vivo quercetin caused significant apoptosis and reduced tumor cell proliferation. Our data provide evidence that oral administration of quercetin was capable of inhibiting growth of orthotopic pancreatic tumors in a nude mouse model. These data suggest a possible benefit of quercetin in patients with pancreatic cancer."



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"Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation Duo J, Ying GG, Wang GW, Zhang L. Quercetin inhibits human breast cancer cell proliferation and induces apoptosis via Bcl-2 and Bax regulation. Mol Med Rep. 2012 Jun;5(6):1453-6. doi: 10.3892/mmr.2012.845. Epub 2012 Mar 22. PubMed PMID: 22447039. Breast cancer is a disease in which cancer cells form in the tissues of the breast. The present study aimed to explore the effect of the flavonoid compound quercetin on the growth and apoptosis of human breast cancer cells. Varying concentrations (12.5, 25, 50, 100, 200 µM) of quercetin were applied to cultured MCF-7 human breast cancer cells for defined lengths of time. At 50 to 200 µM doses, quercetin significantly inhibited the proliferation of MCF-7 cells assessed by MTT colorimetry, in both dose- and time-dependent manners (P < 0.05). The compound also increased apoptosis after 48 h of exposure (P < 0.05). Furthermore, following quercetin treatment Bcl-2 expression decreased significantly while Bax expression increased significantly (P < 0.05). In brief, quercetin inhibits cell growth and induces apoptosis in MCF-7 human breast cancer cells. The mechanisms behind these effects may stem from the downregulation of Bcl-2 protein expression and upregulation of Bax expression.



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"Molecular mechanisms of action of quercetin in cancer: recent advances Kashyap D, Mittal S, Sak K, Singhal P, Tuli HS. Molecular mechanisms of action of quercetin in cancer: recent advances. Tumour Biol. 2016 Oct;37(10):12927-12939. Epub 2016 Jul 22. Review. PubMed PMID: 27448306. In the last few decades, the scientific community has discovered an immense potential of natural compounds in the treatment of dreadful diseases such as cancer. Besides the availability of a variety of natural bioactive molecules, efficacious cancer therapy still needs to be developed. So, to design an efficacious cancer treatment strategy, it is essential to understand the interactions of natural molecules with their respective cellular targets. Quercetin (Quer) is a naturally occurring flavonol present in many commonly consumed food items. It governs numerous intracellular targets, including the proteins involved in apoptosis, cell cycle, detoxification, antioxidant replication, and angiogenesis. The weight of available synergistic studies vigorously fortifies the utilization of Quer as a chemoprevention drug. This extensive review covers various therapeutic interactions of Quer with their recognized cellular targets involved in cancer treatment."



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"The multifaceted role of curcumin in cancer prevention and treatment Shanmugam MK, et al. The multifaceted role of curcumin in cancer prevention and treatment. Molecules. 2015 Feb 5;20(2):2728-69. doi: 10.3390/molecules20022728. Review. PubMed PMID: 25665066. Despite significant advances in treatment modalities over the last decade, neither the incidence of the disease nor the mortality due to cancer has altered in the last thirty years. Available anti-cancer drugs exhibit limited efficacy, associated with severe side effects, and are also expensive. Thus identification of pharmacological agents that do not have these disadvantages is required. Curcumin, a polyphenolic compound derived from turmeric (Curcumin longa), is one such agent that has been extensively studied over the last three to four decades for its potential anti-inflammatory and/or anti-cancer effects. Curcumin has been found to suppress initiation, progression, and metastasis of a variety of tumors. These anti-cancer effects are predominantly mediated through its negative regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic molecules. It also abrogates proliferation of cancer cells by arresting them at different phases of the cell cycle and/or by inducing their apoptosis. The current review focuses on the diverse molecular targets modulated by curcumin that contribute to its efficacy against various human cancers."



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"Curcumin (Turmeric) and cancer Unlu A, Nayir E, Dogukan Kalenderoglu M, Kirca O, Ozdogan M. Curcumin (Turmeric) and cancer. J BUON. 2016 Sept-Oct;21(5):1050-1060. Review. PubMed PMID: 27837604. Curcumin is a substance obtained from the root of the turmeric plant, which has the feature of being a yellow or orange pigment. It is also the main component of curry powder commonly used in Asian cuisine. Curcumin, a substance that has had an important place in traditional Indian and Chinese medicines for thousands of years, has been the center of interest for scientific studies especially in the field of cancer treatment for several years. Laboratory studies have presented some favorable results in terms of curcumin's antioxidant, antiinflammatory and anticancer properties in particular. However, since such findings have yet to be confirmed in clinical studies, its effect on humans is not clearly known. Therefore, when its advantages in terms of toxicity, cost and availability as well as the favorable results achieved in laboratory studies are considered, it would not be wrong to say that curcumin is a substance worth being studied. However, for now the most correct approach is to abstain from its use for medical purposes due to lack of adequate reliable evidence obtained from clinical studies, and because of its potential to interfere with other drugs."



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"Curcumin in various cancers Shehzad A, Lee J, Lee YS. Curcumin in various cancers. Biofactors. 2013 Jan-Feb;39(1):56-68. doi: 10.1002/biof.1068. Epub 2013 Jan 10. Review. PubMed PMID: 23303705. Curcumin (diferuloylmethane), an active constituent of turmeric, is a well-described phytochemical, which has been used since ancient times for the treatment of various diseases. The dysregulation of cell signaling pathways by the gradual alteration of regulatory proteins is the root cause of cancers. Curcumin modulates regulatory proteins through various molecular mechanisms. Several research studies have provided in-depth analysis of multiple targets through which curcumin induces protective effects against cancers including gastrointestinal, genitourinary, gynecological, hematological, pulmonary, thymic, brain, breast, and bone. The molecular mechanisms of action of curcumin in treating different types of cancers remain under investigation. The multifaceted role of this dietary agent is mediated through its inhibition of several cell signaling pathways at multiple levels. Curcumin has the ability to inhibit carcinogenicity through the modulation of the cell cycle by binding directly and indirectly to molecular targets including transcription factors (NF-kB, STAT3, β-catenin, and AP-1), growth factors (EGF, PDGF, and VEGF), enzymes (COX-2, iNOS, and MMPs), kinases (cyclin D1, CDKs, Akt, PKC, and AMPK), inflammatory cytokines (TNF, MCP, IL-1, and IL-6), upregulation of proapoptotic (Bax, Bad, and Bak) and downregulation of antiapoptotic proteins (Bcl(2) and Bcl-xL). A variety of animal models and human studies have proven that curcumin is safe and well tolerated even at very high doses. This study elaborates the current understanding of the chemopreventive effects of curcumin through its multiple molecular pathways and highlights its therapeutic value in the treatment and prevention of a wide range of cancers."



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"Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively? Ravindran J, Prasad S, Aggarwal BB. Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively? The AAPS Journal. 2009;11(3):495-510. doi:10.1208/s12248-009-9128-x. Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these agents are highly expensive and thus not affordable for most. Moreover, such agents cannot be used for cancer prevention. Traditional medicines are generally free of the deleterious side effects and usually inexpensive. Curcumin, a component of turmeric (Curcuma longa), is one such agent that is safe, affordable, and efficacious. How curcumin kills tumor cells is the focus of this review. We show that curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). How curcumin selectively kills tumor cells, and not normal cells, is also described in detail."



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"New perspectives of curcumin in cancer prevention Park W, Amin AR. R, Chen ZG, Shin DM. New perspectives of curcumin in cancer prevention. Cancer prevention research (Philadelphia, Pa). 2013;6(5):387-400. doi:10.1158/1940-6207.CAPR-12-0410. Numerous natural compounds have been extensively investigated for their potential for cancer prevention over decades. Curcumin, from Curcuma longa, is a highly promising natural compound that can be potentially used for chemoprevention of multiple cancers. Curcumin modulates multiple molecular pathways involved in the lengthy carcinogenesis process to exert its chemopreventive effects through several mechanisms: promoting apoptosis, inhibiting survival signals, scavenging reactive oxidative species (ROS), and reducing the inflammatory cancer microenvironment. Curcumin fulfills the characteristics for an ideal chemopreventive agent with its low toxicity, affordability, and easy accessibility. Nevertheless, the clinical application of curcumin is currently compromised by its poor bioavailability. Here we review the potential of curcumin in cancer prevention, its molecular targets, and action mechanisms. Finally, we suggest specific recommendations to improve its efficacy and bioavailability for clinical applications."



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"Therapeutic Potential of Curcumin for the Treatment of Brain Tumors Klinger NV, Mittal S. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors. Oxid Med Cell Longev. 2016;2016:9324085. Epub 2016 Oct 11. Review. PubMed PMID: 27807473; PubMed Central PMCID: PMC5078657. Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors."



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"Molecular Mechanisms of Anti-metastatic Activity of Curcumin Deng YI, Verron E, Rohanizadeh R. Molecular Mechanisms of Anti-metastatic Activity of Curcumin. Anticancer Res. 2016 Nov;36(11):5639-5647. Review. PubMed PMID: 27793885. Cancer is the leading cause of death worldwide. Although cancer occurs as a localized disease, its morbidity and mortality rates remain high due to the ability of cancer cells to break-off from the primary tumor and spread to distant organs. Currently, chemotherapy is the main treatment for cancer; however, the increase in proportion of drug-resistant cancer cells and unpleasant side-effects of chemotherapy are still the major challenges in cancer therapy. Curcumin is a natural polyphenol compound and the main bioactive constituent of Indian spice turmeric, widely used in Indian and Chinese medicines. Curcumin has well-known therapeutic actions, including anti-inflammatory, anti-microbial, anti-oxidant and anti-cancer properties. Curcumin induces cancer cell apoptosis through regulating various signaling pathways and arresting tumor cell cycle. Curcumin's therapeutic/ preventative actions on metastatic cancers have not been yet fully understood and studied. The present review explores the potential anti-metastatic mechanisms of curcumin, including inhibition of transcription factors and their signaling pathways (e.g., NF-κB, ApP-1 and STAT3), inflammatory cytokines (e.g., CXCL1, CXCL2, IL-6, IL-8), multiple proteases (e.g., uPA, MMPs), multiple protein kinases (e.g., MAPKs, FAK), regulation of miRNAs (e.g., miR21, miR181b) and heat shock proteins (HLJ1). In addition, possible synergistic actions of combination therapy of curcumin with current chemotherapies are discussed in this review."



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