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Reversal of multidrug resistance in murine fibrosarcoma cells by thioxanthene flupentixol

  • Preclinical Studies
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Summary

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.

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Authors and Affiliations

  1. Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, 77030, Houston, TX, USA

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

  2. Research and Development, SmithKline Beecham Pharmaceuticals, King of Prussia, 19406, PA, USA

    George Poste

Authors
  1. Dominic Fan
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  2. George Poste
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  3. Christopher Seid
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  4. Laura E. Earnest
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  5. Todd Bull
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  6. Rosemary K. Clyne
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  7. Isaiah J. Fidler
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Fan, D., Poste, G., Seid, C. et al. Reversal of multidrug resistance in murine fibrosarcoma cells by thioxanthene flupentixol. Invest New Drugs 12, 185–195 (1994). https://doi.org/10.1007/BF00873959

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