Phorbol ester-induced P-glycoprotein phosphorylation and functionality in the HTB-123 human breast cancer cell line.
The discordance between P-glycoprotein (P-gp) expression and functionality [as measured by the efflux of doxorubicin (DOX)] was analyzed in a DOX-sensitive human breast cancer cell line (HTB-123) with high reactivity against four P-gp specific monoclonal antibodies (C219, MRK-16, UIC2, and 4E3). Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analyses confirmed the overexpression of MDR1 mRNA and P-gp in this cell line. However, incubation of cells with efflux blockers, verapamil (VPL) or dipyridamole (DPD), did not enhance cellular (DOX) accumulation or cytotoxicity. Upon incubation with 12-O-tetradecanoylphorbol-13-acetate (TPA), HTB-123 cells retained less DOX than control cells and were sensitive to the efflux blockers verapamil or dipyridamole. These observations suggest that 12-O-tetradecanoylphorbol-13-acetate-induced P-gp phosphorylation may be associated with induction of P-gp-mediated drug efflux in the HTB-123 cell line.
Ramachandran
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Department of Radiation Oncology and Sylvester Cancer Center, University of Miami School of Medicine, FL 33136, USA.
Kunikane
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You
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Krishan
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D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology*; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002273:Carcinogens; D004317:Doxorubicin; D013755:Tetradecanoylphorbol Acetate