Estrone and 17β‐Estradiol Reverse Breast Cancer Resistance Protein‐mediated Multidrug Resistance

Abstract

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 l7β‐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 17β‐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.