Metformin: a Panacea for Diabetes, Cancer and Aging?

Researchers at Université de Montreal and McGill University showed that the anti-diabetic drug metformin had an inhibitory effect on some inflammatory cytokines seen in cellular senescence, in prostate cancer.  Metformin is the most widely prescribed drug for people who suffer from diabetes type II.  Proven safe in many circumstances, including for people with heart problems, its main effect is a lowering of hepatic glucose production.  However, it has also been shown to reduce LDL and triglycerides, as well as having antiproliferative effects in breast, colon, ovarian, pancreatic and prostate cancer cell lines.  Further, in mice and worms metformin seems to increase lifespan.

Previous to this experiment, it was known that senescent cells release many cytokines. Though senescence is thought to be an evolutionary means for cancer prevention, these cytokines have been associated with reactive oxygen species and cancer promotion.  Here, metformin was shown to inhibit the effects of the conditioned medium (which promotes cancer cell growth) expressed by senescent cells in prostate cancer.  Specifically, it was shown that metformin blocks the entry of NF-kB into the nucleus.  This inhibits activation of its associated pathway in both senescent and non-senescent cells.  The NF-kB pathway is highly associated with aging and inflammation.

So, the paradox becomes – how to mitigate the senescent effects of the tumour suppressive genes without losing the anticancer properties they bring to the cell.  Well, it seems that metformin, by reducing certain cytokines associated with IKK alpha/beta kinases whilst not inhibiting the function of p38MAPK and the interferons that come from it, may be the insight needed for the scientific world to begin tackling aging and cancer in one fell swoop.


The original research paper was published in: Aging Cell, June 2013

 

Leave a Reply

Your email address will not be published. Required fields are marked *