Sesquiterpene Curzerenone Activates Apoptotic Signaling and Attenuates PI3K/AKT/mTOR Signaling in HepG2 Cells by Triggering Oxidative Stress

Background/Purpose Curzerenone is a sesquiterpene primarily isolated from Curcuma zedoaria rhizomes, identified for its diverse therapeutic efficacy. Recent studies have highlighted curzerenone’s potential anti-cancer, inflammatory attenuating, and anti-oxidant properties. Current research was conducted to investigate the anti-cancer potency of curzerenone on hepatic carcinoma cells. Methods Curzerenone anti-oxidant potency was initially assessed in vitro using ferric reducing anti-oxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. Human liver cancer cell line (HepG2) and Vero cell lines were utilized to assess cytotoxic effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 2′,7′-Dichlorofluorescin diacetate (DCFH-DA) staining quantified reactive oxygen species (ROS) generation. Thiobarbituric acid reactive substances (TBARS) assay and anti-oxidant quantification analyzed curzerenone’s impact. Cell adhesion assay evaluated anti-metastatic effects. Apoptotic signaling proteins and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) proteins were quantified in curzerenone-treated HepG2 cells. Results Curzerenone exhibited strong anti-oxidant activity and tumor cell-specific cytotoxicity while remaining non-cytotoxic to normal Vero cells. Treatment increased intracellular ROS levels, decreased anti-oxidant levels, and induced lipid peroxidation in HepG2 cells. It elevated apoptotic signaling and attenuated PI3K/AKT/mTOR signaling, preventing cancer cell viability and division while increasing cell death. Conclusion Results suggest that curzerenone induces oxidative stress, thereby reducing cancer cell survival and promoting apoptosis in hepatocellular carcinoma cells.