Insulin in aging and cancer: antidiabetic drug diabenol as geroprotector and anticarcinogen

Abstract

The effects of new antidiabetic drug Diabenol ® (9-β-diethylaminoethyl-2,3-dihydroimidazo-(1,2-α)benzimidazol dihydrochloride) on life span and spontaneous tumor incidence in NMRI and transgenic HER-2/neu mice as well as on colon carcinogenesis induced by 1,2-dimethylhydrazine in rats are studied. It is shown that treatment with the drug failed influence body weight gain dynamics, food and water consumption and the body temperature, slowed down age-related disturbances in estrous function and increased life span of all and 10% most long-living NMRI mice. The treatment with diabenol inhibited spontaneous tumor incidence and increased the mammary tumor latency in these mice. Diabenol treatment slowed down age-related changes in estrous function in HER-2/neu mice, failed influence survival of these mice and slightly inhibited the incidence and decreased the size of mammary adenocarcinoma metastases into the lung. In rats exposed to 1,2-dimethylhydrazine, treatment with diabenol significantly inhibited multiplicity of all colon tumors, decreased by 2.2 times the incidence of carcinomas in ascending colon and by 3.1 times their multiplicity. Treatment with diabenol was followed by higher incidence of exophytic and well-differentiated colon tumors as compared with the control rats exposed to the carcinogen alone (76.3% and 50%, and 47.4% and 14.7%, respectively). Thus, the drug increases survival and inhibits spontaneous carcinogenesis in mice and inhibits colon carcinogenesis in rats.