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Grape Compound May Help Curb Cancer
3/31/2008
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Lab findings add to growing evidence of resveratrol’s anti-cancer potential, both alone and as an adjunct to radiation therapy

by Craig Weatherby

Resveratrol’s Metabolic Rewards

In addition to its known anti-cancer properties, resveratrol can extend the life spans of yeasts and flies, which suggests its potential as an anti-aging agent useful in delaying age-related human diseases.


Most recently, experiments in rats showed that large doses of resveratrol can improve the physiological factors underlying metabolism-driven conditions like diabetes, dementia, and cardiovascular disease.


(See “Red Wine Constituent Gives Mice Radical Metabolic Makeovers.”)


But the doses needed to produce positive metabolic effects in rodents were huge.


Unless scientists succeed in current attempts to create a more potent synthetic counterpart, resveratrol’s powerful anti-aging potential may remain more hypothetical than practical.

Red-purple grapes and red wine feature a promising antioxidant factor called resveratrol.


New findings add to the already substantial animal and lab evidence of resveratrol’s potential as an anti-cancer food factor.


In animal and cell studies, resveratrol blocks the process of cancer creation and growth at various stages.


Resveratrol is one of the polyphenol antioxidants abundant in grapes, berries, tea, red cabbage, eggplant, beans, whole grains, and cocoa.


It occurs in all grapes and berries (and peanuts)which produce it to fight off fungibut is most abundant in blue, red, and purple grapes.


Grape agent sickens pancreatic cancer cells, leaves healthy cells alone

Good news for lovers of grapes, grape juice, and red wine comes from researchers at the University of Rochester Medical Center.


Previous studies have shown that resveratrol can prevent cancer-promoting damage to cellular DNA, thanks to its anti-inflammatory effects, antioxidant powers, and its ability to stimulate detoxification genes and suppress internally generated carcinogens (Gatz SA, Wiesmüller L 2008).


Yet despite intense scientific interest in the anti-cancer potential of natural antioxidants, some physicians are concerned that dietary antioxidants might actually protect tumors.


Fortunately, the results of a new study showed that resveratrol increases the damage that radiation therapy does to malignant cells while protecting normal tissue from its harmful effects.


Antioxidants vs. cancer: A double-edged sword?

As we noted, some doctors fear that dietary antioxidants might actually protect tumors. This concern stems from three facts:

  • Immune system cells sometimes attack cancer cells by emitting free radicals: the unstable oxygen compounds that antioxidants normally neutralize.
  • Much of the damage done to cancer cells by radiation therapy comes from the free radicals generated by ionizing radiation. (Compared with healthy cells, cancer cells are usually more vulnerable to free radicals.)
  • Many antioxidants—including resveratrol—can, in the presence of metal ions such as copper,  become “pro-oxidants” that break cellular DNA.

But new research indicates that their pro-oxidant effects could explain many of the anti-cancer and cancer-preventive properties of plant polyphenols such as resveratrol (de la Lastra CA, Villegas I 2007).


And as the new study shows with regard to selective disabling of cancer cells’ mitochondria, this pro-oxidant effect of polyphenols probably occurs only (or primarily) in cancer cells.


This hypothesis is supported by the well-documented anti-cancer effects of polyphenol-rich fruit extracts on tumors in animals and cell tests.

As team leader Paul Okunieff, M.D. put it, “Resveratrol seems to have a therapeutic gain by making tumor cells more sensitive to radiation and making normal tissue less sensitive” (UR 2008).


What's more, Dr. Okunieff’s team found that resveratrol selectively cripples the cellular energy centers (mitochondria) of pancreatic cancer cells, while leaving healthy cells untouched.


The mitochondria of healthy and cancer cells alike contain their own DNA, and can supply the cell with energy as long as the DNA is intact, allowing these minuscule organelles to function properly.


If resveratrol can throw a monkey wrench into the workings of pancreatic cancer cells’ mitochondria, it may keep the tumor from growing.


Radiation + resveratrol = anti-cancer gains

The Rochester team divided pancreatic cancer cells into two groupsa) exposed to resveratrol or b) not exposed to resveratroland treated both groups with the kind of ionizing radiation used on pancreatic cancer patients:


The cells were exposed to doses of resveratrol (50 mg/ml) somewhat higher than the concentrations found in red wine (30 mg/ml). The researchers believe that it would be safe for a patient to take the higher dose as long as a physician is monitoring the results.


They measured the activity of the mitochondria in the cells treated with resveratrol, and also measured apoptosis (cell “suicide”), the level of free radicals in the cells, and how the cell membranes responded to the antioxidant.


The experiment yielded several positive results in the cancer cells exposed to resveratrol:

  • Reduced the function of proteins in pancreatic cancer cell membranes that pump chemotherapy drugs out of the cell, thereby making the cells more vulnerable to drug treatments.
  • Triggered the production of free radicals, to which cancer cells are more vulnerable.
  • Promoted apoptosis (cell “suicide”), likely as the result of increased production of free radicals.
  • Depolarized the mitochondrial membranes, which indicates a decrease in the cell’s potential to function. (Radiation treatment alone does not injure cancer cells’ mitochondrial membranes as much).

As Dr. Okunieff said, “While additional studies are needed, this research indicates that resveratrol has a promising future as part of the treatment for cancer.”


Okunieff, who is a radiation oncologist, noted that drinking red wine during chemotherapy or radiation is “not contraindicated”.


He said that if a patient already drinks red wine moderately, most physicians would not tell the patient to give it up during treatment.


But Dr. Okunieff believes that the better choice would be to eat red and purple grapes or drink purple grape juice, thereby avoiding the negative health effects of over-consuming alcohol.


Note: Resveratrol is also abundant in a Chinese medicinal root called hu zhang (Polygonum cuspidatum), which is often the source of resveratrol in dietary supplements.



Sources

  • Gatz SA, Wiesmüller L. Take a break–resveratrol in action on DNA. Carcinogenesis. 2008 Feb;29(2):321-32. Epub 2008 Jan 3.
  • Khan N, Afaq F, Mukhtar H. Cancer chemoprevention through dietary antioxidants: progress and promise. Antioxid Redox Signal. 2008 Mar;10(3):475-510.
  • University of Rochester (UR). Mounting Evidence Shows Red Wine Antioxidant Kills Cancer. Accessed online March 30, 2008 at  http://www.urmc.rochester.edu/pr/news/pdf.cfm?id=1934
  • Reagan-Shaw S, Mukhtar H, Ahmad N. Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells. Photochem Photobiol. 2008 Mar-Apr;84(2):415-21. Epub 2008 Jan 23.
  • Sun W, Wang W, Kim J, Keng P, Yang S, Zhang H, Liu C, Okunieff P, Zhang L. Anti-cancer effect of resveratrol is associated with induction of apoptosis via a mitochondrial pathway alignment. Adv Exp Med Biol. 2008;614:179-86.
  • Zunino SJ, Storms DH. Resveratrol-induced apoptosis is enhanced in acute lymphoblastic leukemia cells by modulation of the mitochondrial permeability transition pore. Cancer Lett. 2006 Aug 18;240(1):123-34. Epub 2005 Oct 13.
  • de la Lastra CA, Villegas I. Resveratrol as an antioxidant and pro-oxidant agent: mechanisms and clinical implications. Biochem Soc Trans. 2007 Nov;35(Pt 5):1156-60. Review.
  • Das S, Das DK. Anti-inflammatory responses of resveratrol. Inflamm Allergy Drug Targets. 2007 Sep;6(3):168-73. Review.
  • Holme AL, Pervaiz S. Resveratrol in cell fate decisions. J Bioenerg Biomembr. 2007 Feb;39(1):59-63. Review.
  • Athar M, Back JH, Tang X, Kim KH, Kopelovich L, Bickers DR, Kim AL. Resveratrol: a review of preclinical studies for human cancer prevention. Toxicol Appl Pharmacol. 2007 Nov 1;224(3):274-83. Epub 2007 Jan 3. Review.
  • Shankar S, Singh G, Srivastava RK. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci. 2007 Sep 1;12:4839-54. Review.

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