Growth inhibition of multi-drug-resistant breast cancer cells by 2-methoxyoestradiol-bis-sulphamate and 2-ethyloestradiol-bis-sulphamate.

Abstract

There is currently considerable interest in the use of the endogenous oestrogen metabolite, 2-methoxyoestradiol (2-MeOE2) for the treatment and prevention of breast cancer. We have previously shown that sulphamoylation of 2-MeOE2 and related derivatives greatly enhances their ability to inhibit the proliferation of ER+ and ER- breast cancer cells. In this study, we have compared the abilities of 2-methoxyoestradiol-bis-sulphamate (2-MeOE2bisMATE) and 2-ethyloestradiol-bis-sulphamate (2-EtE2bisMATE) with that of 2-MeOE2 to inhibit the proliferation of breast cancer cells when grown on three different substrata: plastic, collagen I and Matrigel. The human breast cell line MCF-7 was utilised for these studies together with its doxorubicin resistant variant, MCF-7 DOX40 and mitoxantrone resistant variant, MCF-7 MR, as a longitudinal model of in vitro drug resistance. On a plastic substratum all three cell lines were sensitive to the effects of 2-MeOE2bisMATE and 2-EtE2bisMATE whereas MCF-7 cells and the MCF-MR variant cells were resistant to the effects of 2-MeOE2 at 1 microM. The sensitivity of the cell lines to those compounds also remained significant when grown on more physiological substrata. All of the drugs tested arrested cells in the G2/M phase of the cell cycle. The finding that breast cancer cells that are resistant to conventional chemotherapeutic agents remain sensitive to 2-substituted oestrogen sulphamates offers considerable potential for the treatment of women with drug-resistant breast cancer.

• Authors: R N Suzuki, S P Newman, A Purohit, M P Leese, B V L Potter, M J Reed
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 84 Issue 2-3 Pg. 269-78 (Feb 2003) ISSN: 0960-0760 [Print] England
• PMID: 12711013 (Publication Type: Journal Article)

Chemical References

• 2-ethyloestradiol-bis-sulfamate
• Biocompatible Materials
• Drug Combinations
• Laminin
• Plastics
• Proteoglycans
• Sulfonic Acids
• matrigel
• 2-methoxyestriol
• Estradiol
• 2-Methoxyestradiol
• Collagen
• sulfamic acid
• Estriol

Topics

• 2-Methoxyestradiol
• Biocompatible Materials (pharmacology)
• Breast Neoplasms (drug therapy)
• Cell Cycle
• Cell Division
• Collagen (pharmacology)
• Drug Combinations
• Estradiol (analogs & derivatives, pharmacology)
• Estriol (analogs & derivatives, pharmacology)
• G2 Phase
• Humans
• Laminin (pharmacology)
• Mitosis
• Models, Chemical
• Plastics (pharmacology)
• Proteoglycans (pharmacology)
• Sulfonic Acids (metabolism, pharmacology)
• Tumor Cells, Cultured