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

Abstract

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 microM) 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.

• Authors: A Purohit, H A Hejaz, L Walden, L MacCarthy-Morrogh, G Packham, B V Potter, M J Reed
• Journal: International journal of cancer (Int J Cancer) Vol. 85 Issue 4 Pg. 584-9 (Feb 15 2000) ISSN: 0020-7136 [Print] United States
• PMID: 10699934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• 2-methoxyoestrone-3-O-sulphamate
• Antineoplastic Agents, Hormonal
• Hydroxyestrones
• Receptors, Estrogen
• Estrone
• Methylnitrosourea
• 2-methoxyestrone

Topics

• Animals
• Antineoplastic Agents, Hormonal (therapeutic use, toxicity)
• Breast Neoplasms (pathology)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Estrone (analogs & derivatives, therapeutic use, toxicity)
• Female
• G2 Phase
• Humans
• Hydroxyestrones (therapeutic use, toxicity)
• Mammary Neoplasms, Experimental (chemically induced, drug therapy, pathology)
• Methylnitrosourea
• Mitosis
• Rats
• Receptors, Estrogen (analysis)
• Tumor Cells, Cultured