title: Dihydromyricetin suppresses the proliferation of hepatocellular carcinoma cells by inducing G2/M arrest through the Chk1/Chk2/Cdc25C pathway.
abstract: The aim of the present study was to evaluate the antitumor mechanism of dihydromyricetin (DHM). Results showed that DHM significantly inhibited cell viability of HepG2 and Hep3B cells in a dose-dependent manner. DHM induced G2/M cell-cycle arrest in HepG2 and Hep3B cells by altering the expression of cell cycle proteins such as cyclin A, cyclin B1, Cdk1, p53, Cdc25c, p-Cdc25c Chk1 and Chk, which are critical for G2/M transition. Knockdown of p53 and Chk1 in HepG2 cells did not affect G2/M phase arrest caused by DHM. Furthermore, G2/M arrest induced by DHM can be disrupted by Chk2 siRNA. These findings indicate that DHM inhibits the growth of hepatocellular carcinoma (HCC) cells via G2/M phase cell cycle arrest through Chk1/Chk2/Cdc25C pathway. The present study identified effects of DHM in G2/M phase arrest in HCC and described detailed mechanisms of G2/M phase arrest by this agent, which may contribute to its overall cancer preventive efficacy in HCC.
authors.affiliation: Laboratory of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Haili
authors.initials: H
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Mingyi
authors.initials: M
authors.lastname: Li
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2 / Q000096:biosynthesis / Q000235:genetics*; D044948:Flavonols / Q000494:pharmacology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D044948:Flavonols; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; C472036:dihydromyricetin