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Friday 01 March 2002

Estrone and 17beta-estradiol reverse breast cancer resistance protein-mediated multidrug resistance.

By: Imai Y, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y.

Jpn J Cancer Res 2002 Mar;93(3):231-5

Breast cancer resistance protein (BCRP), an adenosine triphosphate-binding cassette transporter, confers resistance to a series of anticancer reagents, including mitoxantrone, SN-38 and topotecan. In the present study, we found that estrone and 17beta-estradiol potentiated the cytotoxicity of mitoxantrone, SN-38 and topotecan in BCRP-transduced K562 cells (K562 / BCRP). These estrogens showed only a marginal effect, or none, in parental K562 cells. Estrone and 17beta-estradiol increased the cellular accumulation of topotecan in K562 / BCRP cells, but not in K562 cells, suggesting that these estrogens inhibit the BCRP-mediated drug efflux and overcome drug resistance.

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