title: Fatsioside A‑induced apoptotic death of HepG2 cells requires activation of AMP‑activated protein kinase.
abstract: Hepatocellular carcinoma (HCC) is one of the most malignant types of human primary tumor and has a poor prognosis, therefore, the development of novel therapeutic modalities is necessary. Fatsioside A is a novel baccharane‑type triterpenoid glycoside, which is extracted from the fruits of Fatsia japonica. Previous data has revealed that fatsioside A can exert growth inhibition, cell cycle arrest and induce apoptosis in human glioma cells. However, no detailed investigations have been performed to determine its action on human hepatocellular cells, and the exact mechanisms underlying the induction of apoptosis remain to be elucidated. The aim of the present study was to investigate the anticancer effect of fatsioside A in the HepG2 human HCC cell line, and to investigate the underlying mechanisms by focusing on the AMP‑activated protein kinase (AMPK) signaling cascade. The results of the present study demonstrated that fatsioside A induced apoptotic death of the human HepG2 HCC cells, which was associated with a marked activation of AMPK and increased expression of the downstream acetyl‑CoA carboxylase carboxylase. Inhibition of AMPK by RNA interference or by its inhibitor, compound C, suppressed fatsioside A‑induced caspase‑3 cleavage and apoptosis in the HepG2 cells, while AICAR, the AMPK activator, elicited marked cytotoxic effects. Together, these results suggested that fatsioside A‑induced apoptotic death requires AMPK activation in HepG2 cells.
authors.affiliation: Department of Liver Diseases, Hospital for Infectious Diseases of Jining, Jining, Shandong 272031, P.R. China.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Zheng
authors.affiliation: Department of Radiology, The First People's Hospital of Jining, Jining, Shandong 272031, P.R. China.
authors.forename: Jian-You
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors.forename: Dong-Hui
authors.initials: DH
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D027481:Araliaceae / Q000737:chemistry*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D010936:Plant Extracts / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: C000592854:3,15,18-trihydroxy-18,19-secolupane-12,19-dione 3-O-glucopyranosyl(1-2)glucopyranoside; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D034741:RNA, Small Interfering; D012265:Ribonucleotides; D012503:Saponins; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide