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Issue 8, 2016
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Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer

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Abstract

P-Glycoprotein (P-gp) serves as a therapeutic target for the development of inhibitors to overcome multidrug resistance in cancer cells. Although various screening procedures have been practiced so far to develop first three generations of P-gp inhibitors, their toxicity and drug interaction profiles are still a matter of concern. To address the above important problem of developing safe and effective P-gp inhibitors, we have made systematic computational and experimental studies on the interaction of natural phytochemicals with human P-gp. Molecular docking and QSAR studies were carried out for 40 dietary phytochemicals in the drug-binding site of the transmembrane domains (TMDs) of P-gp. Dietary flavonoids exhibit better interactions with homology modeled human P-gp. Based on the computational analysis, selected flavonoids were tested for their inhibitory potential against P-gp transport function in drug resistant cell lines using calcein-AM and rhodamine 123 efflux assays. It has been found that quercetin and rutin were the highly desirable flavonoids for the inhibition of P-gp transport function and they significantly reduced resistance in cytotoxicity assays to paclitaxel in P-gp overexpressing MDR cell lines. Hence, quercetin and rutin may be considered as potential chemosensitizing agents to overcome multidrug resistance in cancer.

Graphical abstract: Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer

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Publication details

The article was received on 10 Mar 2016, accepted on 07 May 2016 and first published on 09 May 2016


Article type: Paper
DOI: 10.1039/C6MB00187D
Mol. BioSyst., 2016,12, 2458-2470

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    Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer

    S. Mohana, M. Ganesan, B. Agilan, R. Karthikeyan, G. Srithar, R. Beaulah Mary, D. Ananthakrishnan, D. Velmurugan, N. Rajendra Prasad and S. V. Ambudkar, Mol. BioSyst., 2016, 12, 2458
    DOI: 10.1039/C6MB00187D

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