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The effect of 2‐methoxyoestrone‐3‐ O ‐sulphamate on the growth of breast cancer cells and induced mammary tumours
Author(s) -
Purohit Atul,
Hejaz Hatem A.M.,
Walden Laura,
MacCarthyMorrogh Lucy,
Packham Graham,
Potter Barry V.L.,
Reed Michael J.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000215)85:4<584::aid-ijc22>3.0.co;2-q
Subject(s) - breast cancer , mammary gland , cancer , medicine , biology , cancer research , endocrinology , chemistry
2‐Methoxyoestrogens are emerging as a new class of drug that can inhibit tumour growth and angiogenesis. As sulphamoylation of oestrogens enhances their potency and bioavailability we have synthesized 2‐methoxyoestrone‐3‐ O ‐sulphamate (2‐MeOEMATE) and compared its ability to inhibit the proliferation of breast cancer cells with that of 2‐methoxyoestrone (2‐MeOE1). 2‐MeOEMATE (1 μM) inhibited the growth of oestrogen receptor positive MCF‐7 breast cancer cells by 52% whereas 2‐MeOE1 had little effect at this concentration. 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 cells 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‐MeOEMATE induced apoptosis in a significant proportion of treated MCF‐7 cells. In an in vivo study, employing nitrosomethylurea‐induced mammary tumours in intact rats, 2‐MeOE1 (20mg/kg/d, p.o. for 11 days) had little effect on tumour growth. In contrast, the same dose of 2‐MeOEMATE resulted in the almost complete regression of 2/3 tumours over an 11‐day period. We conclude that 2‐MeOEMATE should have considerable therapeutic potential for the treatment of breast tumours. Int. J. Cancer 85:584–589, 2000. © 2000 Wiley‐Liss, Inc.