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

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Article · Volume 22, Issue 1 · pp. 395–406

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

Yujian Tian1, Zhongjie Cao2, Renshuan Li3

  1. 1Department of Hepatobiliary and Pancreatic Surgery, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi Huishan District People’s Hospital, Wuxi, Jiangsu, CHINA.
  2. 2Department of Hepatobiliary and Pancreatic Surgery, Ezhou Central Hospital, Ezhou, Hubei, CHINA.
  3. 3Department of Oncology Thoracic Surgery, Xianyang Hospital of Yan’an University, Xi’an, Shaanxi, CHINA.

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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