title: 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.affiliation: Endocrinology and Metabolic Medicine, Imperial College School of Medicine, St Mary's Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Purohit
authors.forename: H A
authors.initials: HA
authors.lastname: Hejaz
authors.forename: L
authors.initials: L
authors.lastname: Walden
authors.forename: L
authors.initials: L
authors.lastname: MacCarthy-Morrogh
authors.forename: G
authors.initials: G
authors.lastname: Packham
authors.forename: B V
authors.initials: BV
authors.lastname: Potter
authors.forename: M J
authors.initials: MJ
authors.lastname: Reed
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use / Q000633:toxicity*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004970:Estrone / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D016195:G2 Phase; D006801:Humans; D006894:Hydroxyestrones / Q000627:therapeutic use / Q000633:toxicity*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D008770:Methylnitrosourea; D008938:Mitosis; D051381:Rats; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured
chemical_list: C405442:2-methoxyoestrone-3-O-sulphamate; D018931:Antineoplastic Agents, Hormonal; D006894:Hydroxyestrones; D011960:Receptors, Estrogen; D004970:Estrone; D008770:Methylnitrosourea; C003655:2-methoxyestrone