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

ABSTRACT

Background/Objectives: 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 antioxidant properties. Current research was conducted to investigate the anti-cancer potency of curzerenone on hepatic carcinoma cells. Materials and Methods: Curzerenone antioxidant potency was initially assessed in vitro using ferric reducing antioxidant 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 antioxidant 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 antioxidant activity and tumor cell-specific cytotoxicity while remaining non-cytotoxic to normal Vero cells. Treatment increased intracellular ROS levels, decreased antioxidant 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.

KEYWORDS

• Sesquiterpene
• curzerenone
• antioxidant
• human liver cancer cell line hepatocellular carcinoma cells
• oxidative stress
• apoptosis

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• DOI10.1177/09731296251348104Copy

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