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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters / metabolism*
-
Antineoplastic Agents / toxicity*
-
Breast Neoplasms / metabolism*
-
Camptothecin / analogs & derivatives
-
Camptothecin / toxicity
-
Drug Resistance, Multiple*
-
Drug Resistance, Neoplasm*
-
Drug Synergism
-
Estradiol / pharmacology*
-
Estrone / pharmacology*
-
Female
-
Flow Cytometry
-
Humans
-
Irinotecan
-
K562 Cells / drug effects
-
K562 Cells / metabolism
-
Mitoxantrone / toxicity
-
Neoplasm Proteins*
-
Topoisomerase I Inhibitors
-
Topotecan / toxicity
-
Transfection
Substances
-
ABCG2 protein, human
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters
-
Antineoplastic Agents
-
Neoplasm Proteins
-
Topoisomerase I Inhibitors
-
Estrone
-
Estradiol
-
Irinotecan
-
Topotecan
-
Mitoxantrone
-
Camptothecin