Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells


Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to beoverexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin onHDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone SiHaR (derivedfrom SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatininduced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibitedHDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and SiHaR,leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclinD1 and CDK4 were observed. Cisplatin resistance in SiHaR due to over-expression of MRP1 and Pgp1 wasovercome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cellkilling. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatoryproteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, loweringthe chemotherapeutic dose of the drug cisplatin.