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

The effect of 2-methoxyoestrone-3-O-sulphamate on the growth of breast cancer cells and induced mammary tumours
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 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.
0020-7136
584-589
Purohit, A.
244d02b1-a22c-435e-bbae-8cc97d44c733
Hejaz, H.A.
9fc57abe-9afe-48b3-829c-cc1de3549e19
Walden, L.
59e8251a-0967-4565-83e2-8063d48c280b
MacCarthy-Morrogh, L.
b9d71a1b-ea6f-4f15-868f-286950c55204
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Potter, B.V.
0244e337-e9e7-4c24-9750-75b683326c7d
Reed, M.J.
dc770ba6-b5fa-4232-b5d9-c7b51569c5d4
Purohit, A.
244d02b1-a22c-435e-bbae-8cc97d44c733
Hejaz, H.A.
9fc57abe-9afe-48b3-829c-cc1de3549e19
Walden, L.
59e8251a-0967-4565-83e2-8063d48c280b
MacCarthy-Morrogh, L.
b9d71a1b-ea6f-4f15-868f-286950c55204
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Potter, B.V.
0244e337-e9e7-4c24-9750-75b683326c7d
Reed, M.J.
dc770ba6-b5fa-4232-b5d9-c7b51569c5d4

Purohit, A., Hejaz, H.A., Walden, L., MacCarthy-Morrogh, L., Packham, G., Potter, B.V. and Reed, M.J. (2000) The effect of 2-methoxyoestrone-3-O-sulphamate on the growth of breast cancer cells and induced mammary tumours. International Journal of Cancer, 85 (4), 584-589. (doi:10.1002/(SICI)1097-0215(20000215)85:4<584::AID-IJC22>3.0.CO;2-Q).

Record type: Article

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.

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Published date: 2 March 2000

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Local EPrints ID: 157215
URI: http://eprints.soton.ac.uk/id/eprint/157215
ISSN: 0020-7136
PURE UUID: b487108a-7b51-426c-ada6-41208b03f9c0
ORCID for G. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 04 Jun 2010 09:12
Last modified: 14 Mar 2024 02:44

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Contributors

Author: A. Purohit
Author: H.A. Hejaz
Author: L. Walden
Author: L. MacCarthy-Morrogh
Author: G. Packham ORCID iD
Author: B.V. Potter
Author: M.J. Reed

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