Selection and Characterization of Verapamil-Resistant Multidrug Resistant Cells

Danielle F. Canogauci, Fabian S. Seibert, Ahmad R. Safa, John R. Riordan

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Multidrug resistant cells may become acutely sensitive to the calcium channel blocker verapamil, in spite of the fact that its accumulation by these cells is negligible [1]. We selected verapamil-resistant mutants from multidrug resistant Chinese hamster ovary cells. Levels of P-glycoprotein expression and cross-resistance profiles remained unaltered in the verapamil-resistant multidrug resistant cells. As well, a photoactive verapamil analog specifically bound to P-glycoprotein in these cells. We had previously used a photoactive anthracycline to show that calcium antagonists and several anticancer drugs bind to P-glycoprotein at overlapping or interacting sites [2,3]. Verapamil and its analogues no longer inhibit the binding of either anticancer drugs or calcium channel blockers to P-glycoprotein. Sequencing of P-glycoprotein revealed that no change had occurred in the coding sequence as a result of the selection procedure.

Original languageEnglish (US)
Pages (from-to)497-505
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume209
Issue number2
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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