| RESEARCH PAPER |
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| Year : 2013 | Volume
: 4
| Issue : 2 | Page : 103-109 |
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Modulation of multidrug resistance 1 expression and function in retinoblastoma cells by curcumin
Seethalakshmi Sreenivasan1, Sathyabaarathi Ravichandran2, Umashankar Vetrivel2, Subramanian Krishnakumar1
1 L and T Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, Nugambakkam, Chennai, India
2 Centre for Bioinformatics, Vision Research Foundation, Sankara Nethralaya, Nugambakkam, Chennai, India
Correspondence Address:
Umashankar Vetrivel
Centre for Bioinformatics, Vision Research Foundation, Sankara Nethralaya, 18, College Road, Nungambakkam, Chennai - 600 006, Tamil Nadu
India
 Source of Support: Grant from the Indian Council Medical Research (5/13/25/04/NCD.III), Conflict of Interest: None  | Check |
DOI: 10.4103/0976-500X.110882
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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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