Circumvention of multidrug resistance in murine fibrosarcoma and colon carcinoma cells by treatment with the α-adrenoceptor antagonist furobenzazepine

D. Fan, G. Poste, R. R. Ruffolo, Z. Dong, C. Seid, L. E. Earnest, T. E. Campbell, R. K. Clyne, P. J. Beltran, I. J. Fidler

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The purpose of this study was to determine whether agonists and antagonists of α-adrenoceptors that affect calcium fluxes and protein kinase C signal transduction after the chemosensitivity of cancer cells that exhibit multidrug resistance (MDR). The effects of nine α-adrenoceptor agonists or antagonists on the in vitro chemosensitivity of the UV-2237 murine fibrosarcoma and its doxorubicin-selected MDR variants (UV-2237-R1 and UV-2237-R10) were examined. Noncytotoxic concentrations of the α-adrenoceptor antagonist furobenzazepine enhanced the antitumor activity of doxorubicin, actinomycin D, vinblastine and vincristine, but not 5-fluorouracil. Similar effects of furobenzazepine were also observed in recently established doxorubicin-resistant MDR variants of the CT-26 murine colon carcinoma. The chemosensitizing effect of furobenzazepine was associated with an increase in intracellular accumulation of anticancer drugs. Furobenzazepine did not compete with [3H]azidopine for photoaffinity labeling of P-glycoprotein, but it did produce a transient 30% reduction of P-glycoprotein in the MDR cells. These data indicate that furobenzazepine can reverse a P-glycoprotein-mediated experimental MDR phenotype.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalInternational journal of oncology
Volume4
Issue number4
StatePublished - Jan 1 1994
Externally publishedYes

Keywords

  • MDR-reversal
  • P-glycoprotein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fan, D., Poste, G., Ruffolo, R. R., Dong, Z., Seid, C., Earnest, L. E., Campbell, T. E., Clyne, R. K., Beltran, P. J., & Fidler, I. J. (1994). Circumvention of multidrug resistance in murine fibrosarcoma and colon carcinoma cells by treatment with the α-adrenoceptor antagonist furobenzazepine. International journal of oncology, 4(4), 789-798.