Metformin for cancer and aging prevention: is it a time to make the long story short?

Abstract

During the last decade, the burst of interest is observed to antidiabetic biguanide metformin as candidate drug for cancer chemoprevention. The analysis of the available data have shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters (inbred, outbred, transgenic, mutant), spontaneous (non- exposed to any carcinogenic agent) or induced by 16 chemical carcinogens of different classes (polycycIic aromatic hydrocarbons, nitroso compounds, estrogen, etc.), direct or indirect (need metabolic transformation into proximal carcinogen), by total body X-rays and γ- irradiation, viruses, genetic modifications or special high fat diet, using one stage and two-stage protocols of carcinogenesis, 5 routes of the administration of antidiabetic biguanides (oral gavage, intraperitoneal or subcutaneous injections, with drinking water or with diet) in a wide ranks of doses and treatment regimens. In the majority of cases (86%) the treatment with biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed. Very important that there was no any case of stimulation of carcinogenesis by antidiabetic biguanides. It was conclude that there is sufficient experimental evidence of anti-carcinogenic effect of antidiabetic biguanides.

Keywords: aging; antidiabetic biguanides; cancer prevention; metformin; rodents.