Aspirin and resveratrol could prevent cancer by killing tetraploid cells, research shows

February 11, 2014 by Marcia Malory, Medical Xpress report
Coated aspirin tablets. Image: Wikimedia Commons.

(Medical Xpress)—Aspirin and resveratrol kill tetraploid cells in mice and humans, according to a study by Guido Kroemer of the Gustave Roussy Institute in Villejuif, France and his colleagues. Precancerous lesions often contain tetraploid cells; aspirin and resveratrol could help prevent cancer by eradicating these cells. The research appears in the Proceedings of the National Academy of Sciences.

Tetraploid cells contain four copies of each chromosome, rather than the usual two copies. Often, tetraploid cells die as soon as they form. If they don't die instantly, the body's immune system usually kills them. In the early stages of , however, tetraploid cells can be abundant. Scientists have found abnormally large numbers of tetraploid cells in the beginning stages of bronchial, esophageal, gastric, breast, colorectal, cervical and prostate cancer. Inactivating tumor suppressors in in leads to tetraploidization.

While scientists know that destroying tetraploid cells could protect against cancer, until now they haven't been able to find a substance that kills tetraploid cells without harming . DNA-damaging agents don't hurt tetraploid cells. Some substances that inhibit enzymes needed for cell division do destroy tetraploid cells, but they also prevent normal cell division from taking place.

Kroemer and his team wanted to see if aspirin and , both already known to play a role in cancer prevention, would eliminate tetraploid cells without damaging normal, diploid cells. They gave either aspirin or resveratrol, found in red wine, to mice genetically engineered for a predisposition to intestinal cancer. These genetically engineered mice had more tetraploid cells in their intestinal linings than normal mice. When the researchers gave the cancer-prone mice either resveratrol or aspirin, the number of cells in the mice decreased. The likelihood of the mice developing cancer also decreased.

When the team treated cloned tetraploid mouse Lewis , mouse embryonic fibroblasts and human HCT1 16 colorectal carcinoma RKO cells with resveratrol, the tetraploid cells died but diploid cells of the same type survived. Other cytotoxic substances, such as cisplatin, quercetin and paraquat, were more effective at killing diploid HT1 16 parent cells than their tetraploid clones.

Both resveratrol and aspirin activate AMPK, an enzyme associated with cell homeostasis. Kroemer's team believes they cause AMPK overexpression, which leads to the selective destruction of tetraploid cells. Both diploid and tetraploid cells treated with resveratrol or aspirin experienced the same level of AMPK activation; however, only the tetraploid cells died. The researchers think tetraploid cells have a lower tolerance threshold for AMPK expression than diploid do.

Explore further: Researchers witness new type of cell division, use it to battle cancer

More information: Resveratrol and aspirin eliminate tetraploid cells for anticancer chemoprevention, Delphine Lissa, PNAS, DOI: 10.1073/pnas.1318440111

Abstract
Tetraploidy constitutes a genomically metastable state that can lead to aneuploidy and genomic instability. Tetraploid cells are frequently found in preneoplastic lesions, including intestinal cancers arising due to the inactivation of the tumor suppressor adenomatous polyposis coli (APC). Using a phenotypic screen, we identified resveratrol as an agent that selectively reduces the fitness of tetraploid cells by slowing down their cell cycle progression and by stimulating the intrinsic pathway of apoptosis. Selective killing of tetraploid cells was observed for a series of additional agents that indirectly or directly stimulate AMP-activated protein kinase (AMPK) including salicylate, whose chemopreventive action has been established by epidemiological studies and clinical trials. Both resveratrol and salicylate reduced the formation of tetraploid or higher-order polyploid cells resulting from the culture of human colon carcinoma cell lines or primary mouse epithelial cells lacking tumor protein p53 (TP53, best known as p53) in the presence of antimitotic agents, as determined by cytofluorometric and videomicroscopic assays. Moreover, oral treatment with either resveratrol or aspirin, the prodrug of salicylate, repressed the accumulation of tetraploid intestinal epithelial cells in the ApcMin/+ mouse model of colon cancer. Collectively, our results suggest that the chemopreventive action of resveratrol and aspirin involves the elimination of tetraploid cancer cell precursors.

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8 comments

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v3student
not rated yet Feb 12, 2014
very good
baudrunner
not rated yet Feb 12, 2014
It has long been known that resveratrol contributes to elasticity of the aortas and blood vessels, thereby preventing plaque buildup. Not enough is contained in normal red wine to make a significant contribution in that regard. It is nice to know that a resveratrol product exists, and it would make a very positive impact on heart disease statistics were it to be made available as a dietary supplement. That, in combination with amygdalin and "vitamin B17" would constitute a genuinely effective cancer and heart disease preventative.
jamesinraro
not rated yet Feb 13, 2014
The resveratrol supplement used in virtually all of these trials is Transmax-resveratrol. The actual mode of action of Transmax is the down regulation of a protein known as NF Kappa beta, which is over abundant in all solid cancers, the down regulation of an other protein known as P-53, which is absent in cancer cells and which is needed to support apoptosis, and finally Transmax has an anti-angiogenic effect. It prevents the formation of blood vessels required by tumours to feed the cancer. If Transmax were not a dietary supplement it would be hailed as a breakthrough in cancer prevention and treatment. However, because it can not be monopolised by a pharmaceutical company and the FDA prevents Biotivia, its maker from even mentioning its anti-cancer properties it will take a few more years before it is adopted by oncologists.
baudrunner
not rated yet Feb 16, 2014
Over the years I have become steadily more disillusioned by the ineffectiveness of cancer research over the many decades, wherein all those billions of dollars have been spent to find a cure, to reduce cancer rates and even eradicate it altogether. Cancer rates are rising in proportion to population increase, so at the very least those rates should stay the same as population increases, if only to prove that we are on the right track. I'm sorry that cancer research appears to be more important than eliminating cancer.
RealScience
5 / 5 (1) Feb 17, 2014
Drink a lot of red wine for the resveratrol, then take aspirin for the hangover.

(But freeze a piece of you liver first so that you can get a new one grown in a decade or so.)
baudrunner
5 / 5 (2) Feb 21, 2014
To get the full benefit of the resveratrol contained in the ordinary red wine that you buy at your local outlet you would need to drink about 10,000 glasses per day. I say ordinary red wine because if you drank the wine crafted in the ancient tradition, which includes the skins, seeds and pedicals (the little stems attached to the grape) in the fermentation, then you would need to drink a mere six or so glasses per day. This wine is found only in the Gers region of southern France and on the island of Sardinia, where the traditions are maintained. You will probably not be able to find those wines where you live.
RealScience
5 / 5 (1) Feb 21, 2014
To get the full benefit of the resveratrol contained in the ordinary red wine that you buy at your local outlet you would need to drink about 10,000 glasses per day. I say ordinary red wine because if you drank the wine crafted in the ancient tradition, which includes the skins, seeds and pedicals (the little stems attached to the grape) in the fermentation, then you would need to drink a mere six or so glasses per day. This wine is found only in the Gers region of southern France and on the island of Sardinia, where the traditions are maintained. You will probably not be able to find those wines where you live.


Thanks, baudrunner.
Great to know about the Gers and Sardinian wines, and also how to increase resveratrol content when making one's own wine.

I had heard 100 bottles a day of a typical red wine (and hence my attempt at humor with the liver transplant comment).

Six glasses of wine a day is still a lot, but nowhere near as unreasonable as 10,000 or even ~500.
Captain Stumpy
not rated yet Feb 26, 2014
This wine is found only in the Gers region of southern France and on the island of Sardinia, where the traditions are maintained. You will probably not be able to find those wines where you live.

@baudrunner
what about the traditional reds of Italy in the smaller bottlers?

I used to know some of the smaller country bottled red's were still made this way... but the last time I was there was before 2000, so I cannot say about today. (rural Vicenza area and a couple Sicilian makers)
got any modern info on that?

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