A review on repurposing anti-diabetic drugs for the amelioration of betel-nut induced carcinogenesis

Abstract

Betel-nut (BN) chewing is a socially ingrained practice in several populations worldwide, and is the fourth most addictive habit with several detrimental impacts on health. BN is classified as a class I carcinogen, and its use is associated with the development and progression of cancer through various mechanisms such as the production of nitrosamines, increased oxidative stress, activation of the PI3K/Akt/mTOR pathway, inhibition of tumor suppressors and the dysregulation of cellular energetics, apoptosis and autophagy. Several of these mechanisms overlap with the pathogenesis of diabetes mellitus, making anti-diabetic drugs good candidates for drug repurposing as anti-cancer agents. While a large body of experimental evidence has established the effectiveness of the anti-diabetic drug, metformin, as an anti-cancer agent, clinical trials have largely failed to produce promising results. Our own work as well as that of other workers have also indicated the anti-cancer potential of the dipeptidyl peptidase-4 inhibitor, vildagliptin, though the thiazolidinedione, pioglitazone, was found to have more limited effectiveness and also produced ambiguous results in clinical studies. This review focuses on the mechanisms of BN-induced carcinogenesis and the potential of exploring common anti-diabetic drugs for its amelioration.