The effect of 2-methoxyoestrone-3-O-sulphamate on the growth of breast cancer cells and induced mammary tumours

2-Methoxyoestrogens are emerging as a new class of drug that can inhibit tu mour growth and angiogenesis, As sulphamoylation of oestrogens enhances the ir potency and bioavailability we have synthesized 2-methoxyoestrone-3-O-su lphamate (2-MeOEMATE) and compared its ability to inhibit the proliferation of breast cancer cells with that of 2-methoxyoestrone (2-MeOE1). 2-MeOEMAT E (1 mu M) inhibited the growth of oestrogen receptor positive MCF-7 breast cancer cells by 52% whereas 2-MeOE1 had little effect at this concentratio n, 2-MeOEMATE also inhibited the growth of oestrogen receptor negative MDA- MB-231 breast cancer cells. Exposure of cells to 2-MeOEMATE caused them to round up and become detached suggesting that this compound may induce cells to undergo apoptosis, Cell cycle analysis revealed that 2-MeOEMATE caused cells to arrest in the G(2)/M phase with the increase in G(2)/M arrested ce lls being detectable by 12 hr. Exposure of MCF-7 cells to 2 L-MeOEMATE for 24 hr followed by culture in drug-free medium for 24 hr did not reverse the arrest of cells in the G(2)/M phase. TUNEL analysis confirmed that 2-MeOEM ATE induced apoptosis in a significant proportion of treated MCF-7 cells. I n an in vivo study, employing nitrosomethylurea-induced mammary tumours in intact rats, 2-MeOE1 (10 mg/kg/d, p.o. for 11 days) had little effect on tu mour growth, In contrast, the same dose of 2-MeOEMATE resulted in the almos t complete regression of 2/3 tumours over an 11-day period. We conclude tha t 2-MeOEMATE should have considerable therapeutic potential for the treatme nt of breast tumours. Int. J. Cancer 85:584-589, 2000. (C) 2000 Wiley-Liss, Inc.