Reversal of multidrug resistance in murine fibrosarcoma cells by thioxanthene flupentixol

Dominic Fan, George Poste, Christopher Seid, Laura E. Earnest, Todd Bull, Rosemary K. Clyne, Isaiah J. Fidler

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The purpose of this study was to identify calcium channel and calmodulin antagonists effective in increasing the cytotoxic effects of several chemotherapeutic drugs against UV-2237 murine fibrosarcoma MDR cells. Among 8 compounds tested at nontoxic concentrations, flupentixol, a piperazine-substituted thioxanthene, was the most potent in enhancing the cytotoxicity of anticancer drugs commonly associated with the multidrug resistant (MDR) phenotype, such as Adriamycin, actinomycin D, vinblastine, and vincristine, but not 5-fluorouracil, a drug usually unaffected by MDR. The chemosensitizing effects of flupentixol were produced by increasing intracellular drug accumulation via a mechanism unrelated to the binding of the plasma membrane P-glycoprotein.

Original languageEnglish (US)
Pages (from-to)185-195
Number of pages11
JournalInvestigational New Drugs
Volume12
Issue number3
DOIs
StatePublished - Sep 1 1994
Externally publishedYes

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Keywords

  • P-glycoprotein
  • chemosensitization
  • flupentixol
  • multidrug resistance

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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