Inhibition by 9α-fluoromedoroxyprogesterone acetate (FMPA) against mammary carcinoma induced by dimethylbenz[a]anthracene in rats and angiogenesis in the rabbit cornea – comparison with medroxyprogesterone acetate (MPA)

Abstract Medroxyprogesterone acetate (MPA) is currently used therapeutically in the treatment of mammary and endometrial carcinomas. In order to develop a more potent and useful drug, we synthesized the novel compound, 9α-fluoromedoroxyprogesterone acetate (FMPA), by fluorinating MPA, and we also previously reported that FMPA displays more potent anti-angiogenic activity in the chorioallantoic membrane assay than MPA. In the present study, we investigated (1) the effects of FMPA on rat mammary carcinomas induced by dimethylbenz[ a ]anthracene (DMBA) to determine the anti-tumor activity, (2) the effect on angiogenesis in rabbit corneal assays, and (3) compared these results with those for MPA. FMPA inhibited the growth of mammary carcinomas in a dose-dependent manner (7.5, 30 and 120 mg/kg). Almost complete involution of the carcinomas was observed at doses of 30 and 120 mg/kg. MPA also inhibited the growth of carcinomas at doses of 30 and 120 mg/kg, but no involution of carcinomas was observed even at 120 mg/kg. FMPA significantly and MPA to a lesser degree inhibited carcinogenesis at 120 mg/kg within their treatments. In rabbit corneal assays, FMPA significantly inhibited angiogenesis (IC50 value=0.085 μg/pellet). MPA also significantly inhibited angiogenesis (IC50 value=0.60 μg/pellet). From these results, we conclude that FMPA is potentially more effective in the treatment of mammary carcinomas than MPA.