Insulin in aging and cancer: antidiabetic drug Diabenol as geroprotector and anticarcinogen.
The effects of new antidiabetic drug Diabenol (9-beta-diethylaminoethyl-2,3-dihydroimidazo-(1,2-alpha)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.
Popovich
Irina G
IG
Department of Carcinogenesis and Oncogerontology, N.N. Petrov Research Institute of Oncology, St. Petersburg 197758, Russia.
Zabezhinski
Mark A
MA
Egormin
Peter A
PA
Tyndyk
Margarita L
ML
Anikin
Ivan V
IV
Spasov
Alexander A
AA
Semenchenko
Anna V
AV
Yashin
Anatoly I
AI
Anisimov
Vladimir N
VN
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology; D000367:Age Factors; D000375:Aging; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001831:Body Temperature; D001835:Body Weight; D003110:Colonic Neoplasms / Q000188:drug therapy; D005247:Feeding Behavior; D005260:Female; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000502:physiology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009369:Neoplasms / Q000188:drug therapy; D051381:Rats
C501282:9-diethylaminoethyl-2,3-dihydroimidazo(1,2alpha)benzimidazole; D016588:Anticarcinogenic Agents; D001562:Benzimidazoles; D007004:Hypoglycemic Agents; D007328:Insulin; D019813:1,2-Dimethylhydrazine