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    Journal of Pharmacology and PharmacotherapeuticsNOW IN
    Article

    Modulation of multidrug resistance 1 expression and function in retinoblastoma cells by curcumin

    Seethalakshmi Sreenivasan1★, Sathyabaarathi Ravichandran2, Umashankar Vetrivel1★ Corresponding author

    1. 1Subramanian Krishnakumar L and T Department of Ocular Pathology, India.
    2. 2Centre for Bioinformatics, Vision Research Foundation, Sankara Nethralaya, Nugambakkam, Chennai, India.

    CORRESPONDENCE

    Seethalakshmi Sreenivasan

    Subramanian Krishnakumar L and T Department of Ocular Pathology, India.

    Volume 4, Issue 2 · pp. 103–109 · PUBLISHED 2013 · DOI: 10.4103/0976-500X.110882

    View on J Pharmacol. Pharmacother. original site ↗

    ABSTRACT

    Objective: To determine the possible interaction of curcumin with P‑glycoprotein (P‑gp) expression and function by in vitro and in silico studies. Materials and Methods: In this study, curcumin was compared for its potential to modulate the expression and function of P‑gp in Y79 RB cells by western blot, RT‑PCR (reverse transcription polymerase chain reaction) and functional assay. Further, in silico molecular modeling and docking simulations were performed to deduce the inhibitory binding mode of curcumin. Results: Western blot and RT‑PCR analysis decreased the expression of P‑gp in a dose‑dependent manner. The effect of curcumin on P‑gp function was demonstrated by Rhodamine 123 (Rh123) accumulation and efflux study. Curcumin increased the accumulation of Rh123 and decreased its efflux in retinoblastoma (RB) cells. In addition, curcumin inhibited verapamil stimulated ATPase activity and photoaffinity labeling study showed no effect on the binding of 8‑azido‑ATP‑biotin, indicating its interaction at the substrate binding site. Moreover, molecular docking studies concurrently infer the binding of curcumin into the substrate binding site of P‑gp with a binding energy of ‑7.66 kcal/mol. Conclusion: These findings indicate that curcumin suppresses the MDR1 expression and function, and therefore may be useful as modulators of multidrug resistance in RB tumor.

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      Sreenivasan, S., Ravichandran, S., & Vetrivel, U. (2013). Modulation of multidrug resistance 1 expression and function in retinoblastoma cells by curcumin. Journal of Pharmacology and Pharmacotherapeutics, 4(2), 103–109. https://doi.org/10.4103/0976-500X.110882