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Fluoxetine and reversal of multidrug resistance
1Department of Biochemistry, George S. Wise Life Science Faculty, Tel Aviv University, Tel Aviv 69978, Israel
Abstract:
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.
Insights
The antidepressant fluoxetine (Prozac) shows potential in overcoming cancer multidrug resistance (MDR). It acts as a multi-pump agent, suggesting its use as a novel fourth-generation chemosensitizer.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Multidrug resistance (MDR) is a major challenge in cancer chemotherapy.
- ATP-binding cassette (ABC) transporters and cancer stem cells contribute to MDR.
- Existing MDR reversal agents (chemosensitizers) have limitations.
Purpose of the Study:
- To review recent findings on using fluoxetine to modulate cancer MDR.
- To evaluate fluoxetine as a potential fourth-generation chemosensitizer.
- To discuss the mechanisms of MDR and chemosensitization.
Main Methods:
- Review of in vitro and in vivo studies on fluoxetine's MDR-modulating effects.
- Analysis of fluoxetine's mechanism as a single-pump or multi-pump agent.
- Examination of experimental criteria for novel chemosensitizer candidates.
Main Results:
- Fluoxetine demonstrates chemosensitizing activity against multidrug-resistant cancer cells.
- Fluoxetine functions as a multi-pump MDR reversal agent.
- Evidence supports considering fluoxetine a fourth-generation chemosensitizer.
Conclusions:
- Fluoxetine shows promise for overcoming cancer multidrug resistance.
- Further clinical investigation of fluoxetine for MDR modulation is warranted.
- Development of novel chemosensitizers remains a critical need in cancer therapy.
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