C-Phycocyanin inhibits MDR1 through reactive oxygen species and cyclooxygenase-2 mediated pathways in human hepatocellular carcinoma cell line

The effects of C Phycocyanin (C PC) a biliprotein from Spirulina platensis on the regulation of multidrug resistance-1 (MDR1) a poly glycoprotein in human hepatocarcinoma cell line HepG2 were reported The results revealed that a significant down regulation of MDR1 expression in C PC treated HepG2 cells was through reactive oxygen species and cyclooxygenase-2 (COX-2) mediated pathways C-PC in a concentration dependent manner increased the accumulation of doxorubicin in HepG2 cells and enhanced sensitivity of the cells to doxorubicin by 5 folds The induction of MDR1 expression by PGE(2) and its down regulation by C-PC and DPI (Diphenylene iodonium NADPH oxidase inhibitor) or by COX-2 knockdown suggest that the enhanced sensitivity of HepG2 cells to doxorubicin by C-PC is mediated by the down regulation of MDR1 expression Further studies reveal the involvement of NF-kappa B and AP 1 in the C-PC induced down regulation of MDR1 Also the inactivation of the signal transduction pathways involving Akt ERK JNK and p38 by C PC was observed The present study thus demonstrates the efficacy of C-PC in overcoming the MDR1 mediated drug resistance in HepG2 cells by the down regulation of reactive oxygen species and COX 2 pathways via the involvement of NF-kappa B and AP-1 (C) 2010 Elsevier B V All rights reserved