Phorbol ester-induced P-glycoprotein phosphorylation and functionality in the HTB-123 human breast cancer cell line

Cheppail Ramachandran, Hiroshi Kunikane, Wei You, Awtar Krishan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)709-718
Number of pages10
JournalBiochemical Pharmacology
Volume56
Issue number6
DOIs
StatePublished - Sep 15 1998

Keywords

  • Drug efflux
  • Multidrug resistance
  • P-glycoprotein
  • Phorbol ester
  • Phosphorylation

ASJC Scopus subject areas

  • Pharmacology

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