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

doi:10.1007/BF00873959

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

Cancer Biology

Research output: Contribution to journal › Article › peer-review

25 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 language	English (US)
Pages (from-to)	185-195
Number of pages	11
Journal	Investigational New Drugs
Volume	12
Issue number	3
DOIs	https://doi.org/10.1007/BF00873959
State	Published - Sep 1994

Keywords

P-glycoprotein
chemosensitization
flupentixol
multidrug resistance

ASJC Scopus subject areas

Oncology
Pharmacology
Pharmacology (medical)

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10.1007/BF00873959

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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.",

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AU - Fan, Dominic

AU - Poste, George

AU - Seid, Christopher

AU - Earnest, Laura E.

AU - Bull, Todd

AU - Clyne, Rosemary K.

AU - Fidler, Isaiah J.

PY - 1994/9

Y1 - 1994/9

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AB - 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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Reversal of multidrug resistance in murine fibrosarcoma cells by thioxanthene flupentixol

Abstract

Keywords

ASJC Scopus subject areas

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