RESVERATROL Cancers
Can resveratrol be an anti-cancer agent?

As early as 1997, researchers from University of Illinois at Chicago have proposed to use resveratrol as a
cancer-preventive agent. [1] They based on the facts (at that time) that resveratrol was shown to have
anti-cancer activities in assays representing three major stages of carcinogenesis. At that time, resveratrol
was already known as an antioxidant and antimutagen and to be able to induce phase II drug-metabolizing
enzymes (anti-initiation activity). A few animal studies supported their speculation that resveratrol could be
a candidate to treat cancers. Since then, there were many animal studies about how to use resveratrol
lower the risk of having cancers or use resveratrol as an adjuvant agent for chemotherapies. In this article,
I'm going to highlight a few interesting studies:

Observation (Epidemiological Studies)

Trans-resveratrol (RSVL; 3,4',5-trihydroxystilbene), a natural compound found in grapes, berries, peanuts
and red wine exerts certain anticancer roles in different human cancer types. Several epidemiological
studies have revealed that resveratrol is probably one of the active ingredients of wine responsible for its
health benefits such as prevention of vaso-coronary diseases and cancer. Resveratrol acts on the
process of carcinogenesis by affecting the three phases: tumor initiation, promotion and progression
phases and suppresses the final steps of carcinogenesis, i.e. angiogenesis and metastasis. It is also able
to activate apoptosis, to arrest the cell cycle or to inhibit kinase pathways. [2]

Intensifying Anti-cancer Agents

Resveratrol adds to the growth inhibitory/anticancer activity of cisplatin and doxorubicin in vitro and
protects against doxorubicin-induced cardiac toxicity both in vitro and in mice. [3]

Endometrial Cancer/ Human Uterine Cancer Cells

Endometrial cancer is the fourth most prominent cancer among all feminine cancers in the Western world.
At the molecular level, resveratrol has been reported to inhibit cyclooxygenase (COX) expression and/or
activity; in endometrial cancer cells, COX-2 is overexpressed and confers cellular resistance to apoptosis.
Researchers from Université du Québec found that high-doses of resveratrol triggered apoptosis in five
out of six uterine cancer cell lines. [4]

Colon Cancer / HT-29 Colon Cancer Cells

Resveratrol exhibited a variety of molecular events in etoposide-based combination therapy in HT-29
colon cancer cells including the activation of adenosine monophosphate (AMP)-activated protein kinase,
inhibition of cell growth, induction of apoptosis, and reactive oxygen species (ROS) generation. [5]

Breast Cancer / Human Breast Cancer Cells

Researchers from Kuwait University, found resveratrol-induced growth inhibition in T47D human breast
cancer cells was caused by apoptosis in a cell study. Resveratrol-induced apoptosis is associated with the
activation of the p53 in a dose- and a time-dependent manner. [6]

Researchers from China Medical University, Taiwan, found resveratrol significantly
inhibited growth factor heregulin-beta1 (HRG-beta1)-mediated Matrix metalloproteinase (MMP-9)
expression in human breast cancer cells. Resveratrol significantly suppressed HRG-beta1-mediated
phosphorylation of ERK1/2 and invasion of breast cancer cells. [8]

Prostate Cancer / Mouse

Researchers from University of Alabama at Birmingham fed transgenic Adenocarcinoma Mouse Prostate
males with resveratrol (625 mg resveratrol per kg AIN-76A diet) or phytoestrogen-free, control diet
(AIN-76A). They found resveratrol in the diet significantly reduced the incidence of poorly differentiated
prostatic adenocarcinoma by 7.7-fold. [9]

Lung Cancer / Microarray

Researchers from IIT Research Institute showed resveratrol as a potent inhibitor of A549 lung cancer cell
growth based on a microarray gene expression study. [10]

Clinical Study in Human
A phase I study of oral resveratrol (single doses of 0.5, 1, 2.5, or 5 g) was conducted by Leicester
University, UK, in 10 healthy volunteers per dose level. Resveratrol and six metabolites were recovered
from plasma and urine. Peak plasma levels of resveratrol at the highest dose were 539 +/- 384 ng/mL (2.4
micromol/L), which occurred 1.5 h post-dose. Cancer preventive effects of resveratrol in cells in vitro
require levels of at least 5 micromol/L. The results suggest that consumption of high-dose resveratrol
might be insufficient to elicit systemic levels commensurate with cancer preventive efficacy. [7]

Conclusion

Please, note that I listed only a few studies here. There are lots more studies about the anti-cancer
activities of resveratrol. But, most of them were done in vitro and in animal models. It is not sure if
resveratrol works the same way in human. Though the Phase I Study (above) indicates the amount of
resveratrol absorbed in the blood stream may not be sufficient to lower the risk of cancer. However, proper
formulation may overcome the solubility or absorption issues.
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Reference:
[1] Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, Fong HH, Farnsworth NR, Kinghorn
AD, Mehta RG, Moon RC, Pezzuto JM. Cancer chemopreventive activity of resveratrol, a natural product
derived from
grapes. Science. 1997 Jan 10;275(5297):218-20. [2] Delmas D, Lançon A, Colin D, Jannin B, Latruffe N.
Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer. Curr Drug Targets.
2006 Apr;7(4):423-42. [3] Rezk YA, Balulad SS, Keller RS, Bennett JA. Use of resveratrol to improve the
effectiveness of cisplatin and doxorubicin: study in human gynecologic cancer cell lines and in rodent
heart. Am J Obstet Gynecol. 2006 May;194(5):e23-6. Epub 2006 Apr 21. [4] Sexton E, Van Themsche C,
LeBlanc K, Parent S, Lemoine P, Asselin E. Resveratrol interferes with AKT activity and triggers apoptosis
in human uterine cancer cells. Mol Cancer. 2006 Oct 17;5:45. [5] Hwang JT, Kwak DW, Lin SK, Kim HM,
Kim YM, Park OJ. Resveratrol induces apoptosis in chemoresistant cancer cells via modulation of AMPK
signaling pathway. Ann N Y Acad Sci. 2007 Jan;1095:441-8. [6] Alkhalaf M. Resveratrol-induced apoptosis
is associated with activation of p53 and inhibition of protein translation in T47D human breast cancer cells.
Pharmacology. 2007;80(2-3):134-43. Epub 2007 May 29. [7] Boocock DJ, Faust GE, Patel KR, Schinas
AM, Brown VA, Ducharme MP, Booth TD,
Crowell JA, Perloff M, Gescher AJ, Steward WP, Brenner DE. Phase I dose escalation pharmacokinetic
study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol
Biomarkers Prev. 2007 Jun;16(6):1246-52. [8] Tang FY, Chiang EP, Sun YC. Resveratrol inhibits
heregulin-beta1-mediated matrix metalloproteinase-9 expression and cell invasion in human breast cancer
cells. J Nutr Biochem. 2008 May;19(5):287-94. Epub 2007 Jul 24. [9] Harper CE, Patel BB, Wang J,
Arabshahi A, Eltoum IA, Lamartiniere CA. Resveratrol suppresses prostate cancer progression in
transgenic mice. Carcinogenesis. 2007 Sep;28(9):1946-53. Epub 2007 Aug 3. [10] Whyte L, Huang YY,
Torres K, Mehta RG. Molecular mechanisms of resveratrol action in lung cancer cells using dual protein
and microarray analyses. Cancer Res. 2007 Dec 15;67(24):12007-17.
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Herbal / Dietary Supplements / Foods that may lower the risk of certain types of cancer
: Avocados
Dandelion
, Ellagic acid, Oldenlandia, Falcarinol, Fenugreek, Feverfew, Fish Oil, Forskolin, Galangal, Garlic,
Gotu Kola
, Green Tea, Grape Seed Extract, Honokiol, Orange, Isothiocyanates, Linseed Oil, Limes, Lycopene,
Maitake, Milk Thistle, Onion, Peony, Phellinus, Quercetin, Pterostibene, Pycnogenol, Reishi, Rhubarb, Saffron,
Stinging Nettle, Sweet Potatoes, and more.

Drugs listed in this website for chemotherapy:
Xeloda, Avastin, Tykerb,
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zhion@zhion.com) to correct my mistake(s).
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to be accurate. The information is not intended to be a substitute for professional medical advice. It is
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