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Cancer Lett. 2006 Jun 18;237(2):180-7. Epub 2005 Jul 12.

Fluoxetine and reversal of multidrug resistance.

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Department of Biochemistry, George S. Wise Life Science Faculty, Tel Aviv University, Tel Aviv 69978, Israel


This review centers on recent findings with respect to modulating cancer multidrug resistance (MDR) with the well-known antidepressant fluoxetine (prozac). The MDR phenomena and mechanisms are discussed, including the roles of ABC transporters as MDR-pumps and the potential involvement of cancer stem cells. The three generations of MDR reversal agents (chemosensitizers) are reviewed, introducing the concept of single-pump and multi-pump agents. The current status of chemosensitization is summarized, pointing-out the need for additional agents and outlining experimental criteria for testing novel candidates. Major in vitro and in vivo findings are summarized showing that fluoxetine is a chemosensitizer of the multi-pump type, and proposing it be considered a fourth-generation chemosensitizer. In concluding, we contemplate future prospects of modulating MDR in the clinic.

[Indexed for MEDLINE]

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