By: Brianna Choyce
It appears that the battle against cancer is moving in a promising new direction. Numerous epidemiological studies have shown an inverse correlation between diets rich in plant-based foods and the incidence of cancer. Research has identified several naturally-occurring phytochemicals of certain plants which have powerful biological activity and health benefits. Phytochemicals are compounds derived from plants that can be extracted and purified for consumption and supplementation. The mechanisms by which phytochemicals exert their anticancer activity varies among the compounds. Some have even been found to attack cancer in multiple ways. A common theme among the many mechanisms of action of phytochemicals is related to antioxidant activity and ability to suppress DNA damage caused by oxidative stress. Presently, a lot of research is being conducted to investigate the chemotherapeutic and chemopreventive capabilities of phytochemicals and how they may fit into current cancer treatment. Nevertheless, a plethora of completed research has already provided much evidence of the benefits of phytochemicals in cancer. This article will briefly touch on some of the most potent and effective phytochemicals and the proposed mechanisms by which they fight and prevent cancer.
There is an association between increased intake of garlic and reduced risk of several cancers, including gastric, colon, esophageal, pancreatic, and breast cancer. Garlic, or Allium sativum, belongs to a class called Allium vegetables that includes onions, chives, leeks, and scallions. It is utilized in many cultures to enhance flavor in cooking. Garlic is rich in many compounds that have been shown to have health benefits. Examples of such compounds include: arginine, flavonoids, selenium, and sulfur. Garlic compounds have anticarcinogenic and antitumorigenic properties that stem from various attributes, including antibacterial, antioxidant, and detoxification properties, ability to prevent formation of carcinogens, propensity to promote cellular DNA repair, as well as antiproliferative and apoptotic effects . These properties aid in the prevention of initiation of cellular changes that occur in early stages of cancer development, reduction of the uncontrolled division of cancer cells, and enhancement of the body’s ability to identify damaged cells and either repair or destroy them as necessary.
Ginger is a well-known herb prevalent in foods of many cultures and has been used historically for its medicinal benefits in ailments, such as nausea, gastrointestinal discomfort, and pain. The herb contains potent compounds called gingerols and its derivatives, most notably the dehydrated shogaols, that are being extracted and studied for their medicinal properties. These bioactive phenolics possess antioxidant, anti-inflammatory, antifungal, anti-mycobacterial, and anticarcinogenic properties. Several studies have confirmed that gingerols have anti-metastatic properties in cancers of the breast, skin (melanoma), pancreas, prostate, liver, lungs, rectum, stomach, and colon . In summary, gingerols exhibit their anti-metastatic properties through promotion of apoptosis through activation of a certain gene, down-regulation of cancer-promotion genes, and enhancement of the body’s cancer-killing defenses. Studies have highlighted ginger as having promising clinical potential in cancer therapy.
Ginseng is a traditional herbal medicine that has been used for centuries. Ginseng’s pharmacological benefits are due to its biologically active constituent called ginsenosides and their several mechanisms of action . Used historically for its cardiovascular and cognitive benefits, ginger has countless promising health benefits that seem to be overlooked in today’s medicine. Research and studies dating back to the late 1980’s support the use of ginger in oncology. More current studies have even compared its use to traditional chemotherapeutic agents both alone and in conjunction with the traditional chemo agents. Evidence points to ginseng as having anticarcinogenic properties, including inhibition of tumor cell growth, metastasis, promotion of apoptosis, and ability to target and kill cancer stem cells. Studies suggest that ginseng can stimulate cell differentiation and modulate the immune system to enhance cancer fighting abilities.
Turmeric, a spice that has been recognized for centuries for its medicinal attributes, is harvested from the roots of the Curcuma longa plant of the ginger family. Turmeric is the source of curcumin and curcumin can be extracted from the root of the plant. Curcumin has notable antioxidant and anti-inflammatory properties for which it has been recognized worldwide by health professionals and researchers alike. It can aid in oxidative conditions associated with chronic inflammation, such as arthritis and pain, as well as in metabolic syndrome, high cholesterol, heart disease, and anxiety . It is important to note that Curcumin is “Generally Recognized as Safe (GRAS)” by the Food and Drug Administration (FDA). Current research has highlighted the anticarcinogenic activity of curcumin, which is attributed to prevention of tumor initiation, promotion, metastasis, and angiogenesis . This has been studied in a wide range of cancer types, including prostate, breast, lung, skin, liver, thyroid, ovarian, colon, and rectal cancers. The oral bioavailability of curcumin has also been evaluated to pinpoint the most potent form, which is called BCM-95 . At this time, much research is still ongoing in the field of oncology to define the role of turmeric in chemotherapy and chemoprevention, including its suspected benefits in refractory and resistant cancers.
Green Tea Extract
Tea is one of the most commonly consumed beverages globally. The most significant tea in terms of human health benefits is green tea, due to its biologically active polyphenolic compounds called catechins. The predominant polyphenols in green tea include: epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC).These chemicals have significant antioxidant effects, which proves beneficial for many health conditions. Additionally, these polyphenols have shown anti-tumor potential through inhibition of proliferation, induction of apoptosis, and a reduction in the metastatic potential of tumor cells. Polyphenols of green tea have shown evidence of their ability to detoxify the body through activation of certain naturally-occurring enzymes. Green tea is currently being studied in skin, prostate, breast, lung, liver, colon, and pancreatic cancers .
Resveratrol, also a naturally-occurring polyphenolic compound, is found in blueberries, cranberries, nuts, red grapes, and wine. It has been demanding much attention in oncology for its potent antioxidant and anti-inflammatory properties. Studies in human populations have shown that there is at least a 50% reduction in the risk of breast cancer among women who consume grapes rich in the compound . Resveratrol was first recognized for its cancer chemopreventive attributes in 1997 when it was discovered to intervene at all three stages of carcinogenesis, including initiation, promotion, and progression in HL-60 cells . Studies have further evaluated the implications of these findings, investigating the chemopreventive potential of resveratrol in various forms of cancer. Results show anticancer effects of resveratrol supplementation in breast, liver, esophageal, and colon cancers . There is additional research suggesting that resveratrol can provide benefits in autoimmune diseases and conditions related to aging, including Alzheimer’s, diabetes, liver disease, and cardiovascular diseases.
Another naturally-occurring polyphenolic compound called quercetin has shown powerful antioxidant activity. Quercetin belongs to a group of plant pigments called bioflavonoids and gives many fruits and vegetables their color. Among all of the bioflavonoids, quercetin has received special attention because it is exceptionally effective at scavenging free-radicals . It has strong implications in oncology with numerous studies showing promising antiproliferative and apoptotic effects on cancer cells. Studies have shown that quercetin effectively induced apoptosis in human gastric carcinoma and breast cancer cells .
Tocotrienols are a naturally-occurring form of vitamin E that is found in wheat, barley, and some nuts and grains. They are inherently anti-inflammatory and have antioxidant properties. Four forms of anti-aging tocotrienols have been discovered, gamma-tocotrienol being the most heavily studied. This specific form has been proven to target cancer cells by triggering a unique mechanism called senescence. Senescence is a means of causing old, damaged, or non-productive cells to die. Triggering senescence of cancer cells is suggested to be a key component for therapeutic intervention in the eradication of cancer . Both gamma tocotrienol and quercetin, previously discussed, have demonstrated the ability to induce senescence.
Triterpenes are compounds found in apples and olives as well as in olive components (olive tree leaves and olive oil) that have caught much attention recently in cancer therapy and prevention. These compounds have been used historically in traditional Chinese medicine (TCM) for their anti-inflammatory, antiviral, and antibacterial properties   . Triterpenes have shown evidence of anti-tumor mechanisms, including inhibition of tumor cell proliferation, induction of apoptosis of cancer cells, reduction of metastasis, and inhibition of tumor angiogenesis .
Turkey Tail Mushroom
Various mushrooms have been recognized for their medicinal properties. One type of mushroom called the turkey tail mushroom, also known as Trametes versicolor or Coriolus versicolor, has been included in the National Cancer Institute’s database, the Physician Data Query (PDQ). This database is a comprehensive source of cancer information. The PDQ identifies Polysaccharide K as the biologically active component of turkey tail mushrooms and states that this compound is approved for use in treating cancer in Japan. The PDQ further states, “PSK has been studied in patients with gastric cancer, breast cancer, colorectal cancer, and lung cancer. It has been used as adjuvant therapy in thousands of cancer patients since the mid-1970s. PSK has been safely used in people for a long time in Japan and few side effects have been reported”. Clinical trials have shown that PSK can reduce tumor size and metastasis. It was also shown to inhibit the proliferation of cancer cells, improve T-cell function, and induce apoptosis of cancer cells .
The mechanisms by which each of these compounds exert their anticancer activities support a multi-modal attack on cancer ranging from prevention to eradication. Comprehensive attack involves the immune system, cell signaling pathways, reduction of oxidative species, preventing cellular damage, and destructive targeting of cancer cells and their life cycles. An abundance of research is still being conducted to investigate how these phytochemicals may fit into current cancer treatment regimens. In the meantime, research that has already been completed supports the incorporation of these natural ingredients in our diets and supplement regimens. With all of the available research on the benefits of phytochemical use in cancer, there is hope that a new approach to cancer chemotherapy and chemoprevention is on the horizon.
- 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.
- Ray A, Vasudevan S, Sengupta S. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death. PLoS ONE. 2015; 10(9): e0137614. https://doi.org/10.1371/journal.pone.0137614
- Kim J-H. Cardiovascular Diseases and Panax ginseng: A Review on Molecular Mechanisms and Medical Applications. Journal of Ginseng Research. 2012;36(1):16-26. doi:10.5142/jgr.2012.36.1.16.
- Tode T, et al. Inhibitory effects by oral administration of ginsenoside Rh2 on the growth of human ovarian cancer cells in nude mice. J Cancer Res Clin Oncol, 120 (1993), pp. 24-26.
- Mochizuki M, et al. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull. 1995 Sep;18(9):1197-202. PubMed PMID: 8845804.
- Zhu JH, Takeshita T, Kitagawa I, Morimoto K. Suppression of the formation of sister chromatid exchanges by low concentrations of ginsenoside Rh2 in human blood lymphocytes. Cancer Res. 1995 Mar 15;55(6):1221-3. PubMed PMID: 7882311.
- Yun TK, Choi SY. Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prev. 1995 Jun;4(4):401-8. PubMed PMID: 7655337.
- Kim YS, Kim DS, Kim SI. Ginsenoside Rh2 and Rh3 induce differentiation of HL-60 cells into granulocytes: modulation of protein kinase C isoforms during differentiation by ginsenoside Rh2. Int J Biochem Cell Biol. 1998 Mar;30(3):327-38. PubMed PMID: 9611775.
- Hewlings SJ, Kalman DS. Curcumin: A review of its’ effects on human health. Foods. 2017;6(10):92. doi:10.3390/foods6100092.
- Yallapu MM, Jaggi M, Chauhan SC. Curcumin nanomedicine: a road to cancer therapeutics. Current Pharmaceutical Design. 2013;19(11):1994-2010.
- Antony B, et al. A pilot cross-over study to evaluate human oral bioavailability of BCM-95®CG (BiocurcumaxTM), a novel bioenhanced preparation of curcumin. Indian Journal of Pharmaceutical Sciences. 2008;70(4):445-449. doi:10.4103/0250-474X.44591.
- Khan N, Mukhtar H. Cancer and metastasis: prevention and treatment by green tea. Cancer metastasis reviews. 2010;29(3):435-45. doi:10.1007/s10555-010-9236-1.
- Chikara S, et al. Oxidative stress and dietary phytochemicals: Role in cancer chemoprevention and treatment. Cancer Lett. 2018 Jan 28;413:122-34. doi:
10.1016/j.canlet.2017.11.002. Epub 2017 Nov 4. Review. PubMed PMID: 29113871.
- Jang M, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997 Jan 10;275(5297):218-20. PubMed PMID: 8985016.
- Neuhouser ML. Dietary flavonoids and cancer risk: evidence from human population studies. Nutr Cancer. 2004;50(1):1-7. Review. PubMed PMID: 15572291.
- Wang P, et al. Effects of quercetin on the apoptosis of the human gastric carcinoma cells. Toxicol In Vitro. 2012 Mar;26(2):221-8. doi: 10.1016/j.tiv.2011.11.015. Epub 2011 Dec 24. PubMed PMID: 22222411.
- Choi JA, et al. Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int J Oncol. 2001 Oct;19(4):837-44. PubMed PMID: 11562764.
- Malavolta M, et al. Pleiotropic effects of tocotrienols and quercetin on cellular senescence: introducing the perspective of senolytic effects of phytochemicals. Curr Drug Targets. 2016;17(4):447-59. Review. PubMed PMID: 26343116.
- Checker R, et al. Potent anti-inflammatory activity of ursolic acid, a triterpenoid antioxidant, is mediated through suppression of NF-κB, AP-1 and NF-AT. PLoS One. 2012;7(2):e31318. doi: 10.1371/journal.pone.0031318. Epub 2012 Feb 20. PubMed PMID: 22363615; PubMed Central PMCID: PMC3282718.
- Pavlova NI, Savinova OV, Nikolaeva SN, Boreko EI, Flekhter OB. Antiviral activity of betulin, betulinic and betulonic acids against some enveloped and non-enveloped viruses. Fitoterapia. 2003 Jul;74(5):489-92. PubMed PMID: 12837369.
- Scalon Cunha LC, et al. Antibacterial activity of triterpene acids and semi-synthetic derivatives against oral pathogens. Z Naturforsch C. 2007 Sep-Oct;62(9-10):668-72. PubMed PMID: 18069238.
- Zhang W, Men X, Lei P. Review on anti-tumor effect of triterpene acid compounds. J Cancer Res Ther. 2014;10(Suppl 1):14–19. doi: 10.4103/0973-1482.139746.
- PDQ Integrative, Alternative, and Complementary Therapies Editorial Board. Medicinal Mushrooms (PDQ®): Health Professional Version. 2017 Oct 6. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-. Available from: https://www-ncbi-nlm-nih-gov.ezproxy.hsc.usf.edu/books/NBK401261/