title: Estrone and 17beta-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 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.
authors.affiliation: Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research,Toshima-ku, Tokyo 170-8455, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Imai
authors.forename: Satomi
authors.initials: S
authors.lastname: Tsukahara
authors.forename: Etsuko
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuruo
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000633:toxicity*; D001943:Breast Neoplasms / Q000378:metabolism*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000633:toxicity; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000077146:Irinotecan; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D008942:Mitoxantrone / Q000633:toxicity; D009363:Neoplasm Proteins; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000633:toxicity; D014162:Transfection
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D059004:Topoisomerase I Inhibitors; D004970:Estrone; D004958:Estradiol; D000077146:Irinotecan; D019772:Topotecan; D008942:Mitoxantrone; D002166:Camptothecin