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PMID: 7896537 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Reversal of multidrug resistance in murine fibrosarcoma cells by thioxanthene flupentixol.

Investigational new drugs ·Vol. 12 ·No. 3 ·1994-00-00 ·Pages 185-95

Fan D, Poste G, Seid C, Earnest LE, Bull T, Clyne RK, Fidler IJ

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.

MeSH Terms
ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis Animals Antineoplastic Agents/pharmacology Calcium Channel Blockers/pharmacology Calmodulin/antagonists & inhibitors Doxorubicin/pharmacology Drug Interactions Drug Resistance, Multiple Fibrosarcoma Flupenthixol/pharmacology Mice Tumor Cells, Cultured/drug effects
Chemicals
ATP Binding Cassette Transporter, Subfamily B, Member 1 Antineoplastic Agents Calcium Channel Blockers Calmodulin Doxorubicin Flupenthixol
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Fan D
Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Poste G
Seid C
Earnest L E
Bull T
Clyne R K
Fidler I J
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Article Info
Journal
Investigational new drugs
Abbr.
Invest New Drugs
ISSN
0167-6997
DOI
10.1007/BF00873959
Published
1994-00-00
Pages
185-95
Language
English
Region
United States
NLM ID
8309330
Subset
IM
Grants
NCI NIH HHS · CA 16672 · United States
NCI NIH HHS · R35-CA 42107 · United States
External Links
PubMed source DOI: 10.1007/BF00873959 View journal details
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