A new functional role for P-glycoprotein: efflux pump for benzo(alpha)pyrene in human breast cancer MCF-7 cells.
We propose that the cellular burden of certain carcinogens may be mitigated by P-glycoprotein (P-gp), the putative drug efflux pump. In a series of multidrug resistant human breast cancer MCF-7 cells with increasing P-gp expression we examined this hypothesis using benzo(alpha)pyrene, a widely distributed environmental and dietary carcinogen. We found that multidrug resistant cells were cross-resistant to benzo(alpha)pyrene and the rates of efflux for benzo(alpha)pyrene were higher in multidrug resistant cells than in wild type cells. Evidence supporting the involvement of P-gp included the inhibition of azidopine binding to P-gp benzo(alpha)pyrene and the inhibition of benzo(alpha)pyrene efflux by Adriamycin and verapamil. Our findings suggest that P-gp may play a role in the cellular defense to carcinogens. The expression of P-gp and the modulation of its function may affect the susceptibility of normal tissues to transformation by carcinogens.
Laboratory of Nutritional and Molecular Regulation, National Cancer Institute, NIH, Frederick, Maryland 21702.
G C
GC
Yeh
J
J
Lopaczynska
C M
CM
Poore
J M
JM
Phang
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001564:Benzo(a)pyrene / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D001564:Benzo(a)pyrene; D004317:Doxorubicin; D014700:Verapamil