Curcumin circumvent lactate-induced chemoresistance in hepatic cancer cells through modulation of hydroxycarboxylic acid receptor-1

Abstract Curcumin has been demonstrated to affect the chemoresistance in cancer cells of various origins. However, its ability to modulate lactate-induced chemoresistance remains unclear. The Present investigation demonstrates that curcumin inhibits the survival of HepG2 and HuT78 cells and can modulate chemo-susceptibility of HepG2 cells. Experimental simulation of simultaneous and pre-treatment suggest cooperatively between curcumin and anticancer drugs as well as the modulation of molecular regulators. Inhibition of glucose consumption, lactate production, extracellular acidity and augmented level of Nitric oxide were observed. DAPI staining revealed hyper condensation of chromatin in curcumin-treated HepG2 cells. Curcumin also diminished the lactate-induced chemoresistance against doxorubicin in hepatic cancer cells along with down regulation of lactate receptor (hydroxycarboxylic acid receptor-1; HCAR-1/GPR81). Alteration of the extracellular milieu along with inhibited expression of genes (hif-1α, ldh-a, mct-1, mdr-1 and stat-3) and proteins (HIF-1α and HCAR-1) are indicated to be involved in curcumin-induced reversal of chemoresistance in HepG2 cells. Findings of present investigation contribute to knowledge of curcumin mediated chemosensitization and its mechanism.