Synergistic antiproliferative effects of curcumin and celecoxib in hepatocellular carcinoma HepG2 cells

Abstract

Hepatocellular carcinoma (HCC) is still a leading cancer killer in the community. Molecular targeted therapy with celecoxib (CXB) has shown promising antitumor effects; however, its use may be limited due to serious side effects. Curcumin (CUR) has also shown beneficial effects against HCC. Then, it was aimed to investigate the effects of adding CUR to CXB on HCC HepG2 cells. HepG2 cells were treated with CXB and/or CUR at increasing concentrations to investigate synergistic drug interactions, as calculated combination index (CI). Combination treatment effects on cell viability and caspase-3 activation were assessed. The levels of Akt, nuclear factor-kappa B (NF-κB), prostaglandin E₂ (PGE₂), malondialdehyde (MDA), cyclin D1 (CD1), and vascular endothelial growth factor (VEGF) were also evaluated. CXB (3.13-100 μM) and/or CUR (1.25-40 μM) reduced HepG2 cell viability dose-dependently. Nevertheless, lower combined concentrations showed higher synergism (CI < 1) and higher CXB dose reduction index (DRI > 1). Also, the addition of CUR to CXB resulted in increased cytotoxicity and caspase-3 activation, as compared to CXB alone. In addition, the selected combination significantly reduced the levels of Akt, NF-κB, PGE₂, MDA, CD1, and VEGF, as compared to either agent alone. In conclusion, CUR augmented the CXB-mediated antitumor effects in HepG2 cells through, at least in part, antiproliferative, antioxidant, and pro-apoptotic mechanisms. This may allow the further use of CXB at lower concentrations, combined with CUR, as a promising safer targeted strategy for HCC management.

Keywords: Apoptosis; Celecoxib; Curcumin; HepG2; Proliferation.