Fluoxetine and reversal of multidrug resistance.
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.
Peer
Dan
D
Department of Biochemistry, George S. Wise Life Science Faculty, Tel Aviv University, Tel Aviv 69978, Israel
Margalit
Rimona
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors