Red Wine, Painkillers and Cancer

(March 21st, 2014) Mixing alcohol and painkillers has never been touted as a good idea. However, that didn’t stop a team of French scientists from investigating the effect of Aspirin and red wine on cancerous cells. Want to know what they found out? Read on!

Tetraploid cells, or cells carrying four sets of chromosomes opposed to the regular two sets (diploid) in humans, are frequently observed in the initial stages of cancer. Asymmetrical cell division following tetraploidy is believed to lead to aneuploidy (abnormal chromosome number caused by additional or missing chromosomes) and the genomic instability that is characteristic of tumour progression. A team of scientists led by Guido Kroemer of the Gustave Roussy Institute in Villejuif, France, recently showed that the over-the-counter painkiller Aspirin and the red wine component resveratrol are capable of killing mouse and human tetraploid cells.

The anti-cancer activity of both Aspirin and resveratrol has been known from epidemiological studies and clinical trials. Kroemer and his colleagues investigated if this activity extended to the tetraploid precursors of cancer cells. Additionally, they wanted to find out if this action could discriminate between tetraploid and healthy cells, in that regular diploid cells were left unharmed.

The researchers examined tetraploid cells in the intestinal cancer Familial Adenomatous Polyposis (FAP). FAP is an inherited disorder characterised by small abnormalities or polyps on the surface of the intestinal tract. It is caused due to a fault in the APC (Adenomatous Polyposis Coli) gene that under normal conditions codes for the APC tumour suppressor protein. A faulty APC protein is unable to check uncontrolled cell growth and leads to polyp formation that can eventually turn cancerous.

The French scientists cloned tetraploid cells from human colorectal carcinoma cell lines (HCT 116, RKO) and mouse primary epithelial cells lacking the tumour protein p53. P53 is a cell cycle regulator that is vital for preventing genomic mutations. The tetraploid cells were then separately treated with Aspirin and resveratrol in the presence of antimitotic agents (substances that prevent mitosis or cell division) and observed microscopically and counted using cytofluorometry.

Both Aspirin and resveratrol were seen to selectively reduce the formation of tetraploid and ‘high-order polyploid’ (carrying more than four chromosome sets) cells. Moreover, diploid cells survived the treatment without any damage. Importantly, other chemopreventive agents like cisplatin, quercetin and paraquat, killed more diploid HCT 116 cells rather than their tetraploid counterparts.

For the visually inclined, there’re short movies showing the postmitotic apoptosis of HCT 116 tetraploid cells treated with resveratrol here. The cells have been cloned to stably express the green fluorescent protein for easier identification.

Kroemer’s team also looked at the action of Aspirin and resveratrol in the ApcMin/+ mouse model of colon cancer that is genetically predisposed to intestinal cancer. These mice harboured a larger population of tetraploid cells in their intestinal lining in comparison to wild type mice. When either Aspirin or resveratrol was administered to the mice, the frequency of tetraploid cells in the gut lining was seen to reduce. In addition, the odds of the mice developing intestinal tumours also diminished.

The researchers propose that both Aspirin and resveratrol are able to selectively eliminate tetraploid cells via the same underlying mechanism. They do so by activating the enzyme 5' adenosine monophosphate-activated protein kinase (AMPK), causing its overexpression. AMPK is indispensable for the regulation of cellular energy homeostasis due to its ability to perceive fluxes in the cellular AMP: ATP ratio. Among others, it regulates vital intracellular processes such as glucose uptake.

They say that ‘too much of a good thing can sometimes be bad’, and this proves to be lethal in the case of AMPK overexpression for tetraploid cells. The scientists believe that a lower tolerance threshold for AMPK expression leads to the death of tetraploid cells, while diploid cells come out unscathed. This would explain the selective elimination of the tetraploid cells in this study.

The significance of this study is twofold: firstly, it shows that tackling tetraploid precursors of cancer cells can be an effective mode of chemoprevention. Secondly, it sheds light on the mechanism behind the anti-cancer activity of aspirin and resveratrol and proposes a robust molecular explanation for it.

So while mixing painkillers and alcohol is still strongly discouraged, it doesn’t hurt knowing that under the right conditions, the same substances could save your life!

Latika Bhonsle

Photo: Fotolia/Ilka Burckhardt

Last Changes: 05.02.2014

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