Antidiabetic Drugs in Aging and Cancer: Results and Perspectives

ABSTRACT

Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. Insulin/insulin-like growth factor 1 (IGF-1) signaling molecules that have been linked to longevity include daf-2 and InR and their homologues in mammals, and inactivation of the corresponding genes followed by the increase in life span in nematodes, fruit flies and mice. It is possible that the life-prolonging effect of caloric restriction is due to decreasing IGF-1 levels. A search of pharmacological modulators of insulin/IGF-1 signaling pathway mimetic effects of life span extending mutations or calorie restriction could be a perspective direction in regulation of longevity. Some observations suggest that antidiabetic drugs could be promising candidates for both the life span extension and the prevention of cancer. Thus, anticarcinogenic effect of antidiabetic drugs has been demonstrated in relation to spontaneous carcinogenesis in mice and rats, in number different models of chemical carcinogenesis in mice, rats and hamsters, and in radiation carcinogenesis model in rats. Antidiabetic biguanides inhibit the growth of some transplantable tumors in vivo and in vitro. The data on cancer risk in patients treated with antidiabetic drug will be discussed as well.