Synergistic effect of prochlorperazine and dipyridamole on the cellular retention and cytotoxicity of doxorubicin

Awtar Krishan, Kasi S. Sridhar, Caihong Mou, Wilfred D. Stein, Elena Lyubimov, Yang Ping Hu, Hugo Fernandez

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Incubation of drug-resistant human tumor cells with a combination of prochlorperazine and dipyridamole has additive/synergistic effect on the cellular retention and cytotoxicity of doxorubicin. In patients administered a fixed dose of doxorubicin and prochlorperazine with escalating doses of dipyridamole, mean plasma levels of dipyridamole and prochlorperazine achieved were as high as 3.01 ± 0.41 μm and 0.94 ± 0.09 μm, respectively. Plasma samples from patients were analyzed in an in vitro assay to monitor the effect on the cellular retention of tritium-labeled daunorubicin in MDR1-transfected P388 cells. In 22 of 49 of the plasma samples analyzed, the daunorubicin in efflux blocking activity was one-half or greater than that of cells incubated with 12.5 μM verapamil, a well-known efflux blocker. These observations suggest that a combination of prochlorperazine and dipyridamole may enhance cellular doxorubicin retention by blocking efflux while reducing normal tissue toxicity and unwanted side effects in vivo.

Original languageEnglish (US)
Pages (from-to)1508-1517
Number of pages10
JournalClinical Cancer Research
Volume6
Issue number4
StatePublished - Apr 1 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Krishan, A., Sridhar, K. S., Mou, C., Stein, W. D., Lyubimov, E., Hu, Y. P., & Fernandez, H. (2000). Synergistic effect of prochlorperazine and dipyridamole on the cellular retention and cytotoxicity of doxorubicin. Clinical Cancer Research, 6(4), 1508-1517.