title: Caudatin induces cell cycle arrest and caspase-dependent apoptosis in HepG2 cell.
abstract: In the present study, we investigate the anti-cancer activity and mechanism of caudatin, the C-21 steroidal glycosides, on human hepatoma cell line HepG2. The MTT assay and flow cytometry were used to evaluate HepG2 cell proliferation and cell cycle. Annexin-V/PI and DAPI staining were used to investigate cell apoptosis. Western blotting analysis was used to evaluate the expression levels of proteins. It is found that caudatin inhibits HepG2 cell growth and induces of G0/G1 phase arrest in a dose dependent manner, which is associated with a decreased in the expression of cyclinD1 and increased the levels of p21 and p53. HepG2 cells dealing with caudatin showed typical characteristics of apoptosis. Western blotting analysis indicated that the levels of Bcl-2 were down-regulated after caudatin treatment, whereas the expression of Bax was up-regulated. Furthermore, caudatin-induced apoptosis was accompanied by activation of caspase-3, -9, and poly(ADP-Ribose) Polymerase (PARP). Treatment with caudatin also induced phosphorylation of extracellular-signal regulating kinase (ERK) and c-Jun N-terminal kinase (JNK). These results demonstrate that caudatin inhibits cell proliferation via DNA synthesis reduction and induces caspase-dependent apoptosis in HepG2 cell. Activation of ERK and JNK may be involved in caudatin-induced hepatoma cell apoptosis.
authors.affiliation: School of Pharmacy, Taishan Medical University, Chang Cheng Road, Taian, 271016, People's Republic of China.
authors.forename: Hong Rong
authors.initials: HR
authors.lastname: Fei
authors.forename: Hong Lei
authors.initials: HL
authors.lastname: Chen
authors.forename: Ting
authors.initials: T
authors.lastname: Xiao
authors.forename: Geng
authors.initials: G
authors.lastname: Chen
authors.forename: Feng Ze
authors.initials: FZ
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D031105:Cynanchum / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D018517:Plant Roots / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D006027:Glycosides; D019253:Proto-Oncogene Proteins c-bcl-2; D013256:Steroids; D013778:Tetrazolium Salts; D013844:Thiazoles; D051028:bcl-2-Associated X Protein; C570806:caudatin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; C022616:thiazolyl blue