In vitro and In silico studies on inhibitory effects of curcumin on multi drug resistance associated protein (MRP1) in retinoblastoma cells

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Title	In vitro and In silico studies on inhibitory effects of curcumin on multi drug resistance associated protein (MRP1) in retinoblastoma cells
Authors	Seethalakshmi Sreenivasan¹ & Sathyabaarathi Ravichandran², Umashankar Vetrivel²*, Subramanian Krishnakumar¹
Affiliation	¹L&T Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 18, CollegeRoad, Nungambakkam, Chennai-600 006, India; ²Centre for Bioinformatics, Vision Research Foundation, Sankara Nethralaya, 18, College Road, Nungambakkam, Chennai – 600 006, India
Email	vumashankar@gmail.com; *Corresponding authors
Article Type	Hypothesis
Date	Received December 17, 2011; Accepted December 20, 2011; Published January 06, 2012
Abstract	Multi Drug Resistance (MDR) is one of the major causes of chemotherapy failure in human malignancies. Curcumin, the active constituent of Curcuma longa is a proven anticancer agent potentially modulating the expression and function of these MDR proteins. In this study, we attempted to test curcumin for its potential to inhibit the expression and function of multidrug resistance associated protein 1 (MRP1) in retinoblastoma (RB) cell lines through western blot, RT-PCR and functional assays. In silico analysis were also performed to understand the molecular interactions conferred by curucmin on MRP1 in RB cells. Western blot and RT-PCR analysis did not show any correlation of MRP1 expression with increase in concentration of curcumin. However, inhibitory effect of curcumin on MRP1 function was observed as a decrease in the efflux of fluorescent substrate. Moreover, Curcumin did not affect 8-azido-ATP-biotin binding to MRP1 and it also showed inhibition of ATP-hydrolysis stimulated by quercetin, which is indicative of curcumin’s interaction with the substrate binding site of MRP1. Furthermore, homology modelling and docking simulation studies of MRP1 also provided deeper insights into the molecular interactions, thereby inferring the potential binding mode of curcumin into the substrate binding site of MRP1.
Keywords	TCurcumin, ATP-Binding Cassette, Retinoblastoma, Multi-Drug Resistance Protein, Molecular Docking, Binding analysis
Citation	*Sreenivasan et al.* Bioinformation 8(1): 013-019 (2012)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.