A major impediment for cancer chemotherapy is the development of multidrug-resistance
(MDR). Continuous use of chemotherapeutic drugs during cancer therapy induces the expression of PGlycoprotein
(P-gp, MDR1), an ATP dependant transporter, which in turn reduces the intracellular accumulation
of chemotherapeutic drugs leading to MDR. Extensive research over the years has identified
several potential P-gp inhibitors, both synthetic as well as natural origin, to overcome the MDR
during cancer chemotherapy. In this review, we discuss the cellular pathways involved and transcription
factors regulating the expression of P-gp. A number of phytochemicals are reported to inhibit P-gp activity and
MDR1 expression; the structure-activity relationship (SAR) among the phytochemicals for P-gp inhibition and the effect
of these phytochemicals on cellular signaling pathways regulating P-gp expression are discussed in detail. Moreover,
structural biology and mutagenesis studies on P-gp along with docking studies throw light on the structural requirements
for P-gp inhibition. Insight provided in the review about the phytochemicals molecular mechanism and SAR could catalyze
the design of potent P-gp inhibitors in the future and could help to overcome MDR in cancer chemotherapy.
Keywords: Chemotherapy, Multidrug resistance (MDR), P-glycoprotein (P-gp), Phytochemicals, Structure Activity Relationship.
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