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)

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, 9 alpha -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 thr 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 mug/pellet). MPA also significantly inhibited angiogenesis (IC50 value = 0.60 mug/pellet). From these results, we conclude that FMPA is potentially more effective in the treatment of mammary carcinomas than MPA. (C) 2000 Published by Elsevier Science Ireland Ltd. Published by Elsevier Science Ltd.