title: Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate.
abstract: BACKGROUND
  Sodium 4-phenylbutanoate (NaPB) can induce cellular differentiation and cell cycle arrest. However, its potential anticancer properties in hepatocellular carcinoma and influence on normal liver cell are still unclear. We observed the effects of NaPB on growth inhibition, including differentiation and phase growth arrest in normal liver cell line L-02 and hepatocellular carcinoma cell line Bel-7402. Furthermore, we investigated its mechanism in Bel-7402. METHODS; Hepatocellular carcinoma cells Bel-7402 and normal liver cell line L-02 were treated with NaPB at different concentrations. Light microscopy was used to find morphological change in cells. Cell cycle was detected by flow cytometry. Expression of acetylating histone H4 and of histones deacetylase 4 (HDAC4) were determined by Western blot. The expression of P21WAF1/CIP1 and E-cadherin were observed through immunocytochemistry.
  
  
  RESULTS
  NaPB treatment led to time dependent growth inhibition in hepatocellular carcinoma cells Bel-7402. NaPB treatment caused a significant decline in the fraction of S phase cells and a significant increase in G0/G1 cells. NaPB increased the expression of P21(WAF1/CIP1) and E-cadherin in Bel-7402 and significantly decreased the level of HDAC4 in Bel-7402. NaPB significantly improved the level of acetylating histone H4. The normal liver cell line L-02 showed no distinct changes under treatment with NaPB.
  
  
  CONCLUSIONS
  NaPB inhibited the growth of hepatocellular carcinoma cells Bel-7402 and induced partial differentiation through enhancing the acetylating histones. In Bel-7402, the expressions of P21(WAF1/CIP1) and E-cadherin may be related to level of acetylating histones and inhibition of cellular growth. NaPB showed no significant effect on normal liver cells.
authors.affiliation: Department of Medical Intensive Care Unit, Shandong Province Hospital, Affiliated Hospital of Shandong University, Jinan, Shandong 250021, China.
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Meng
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Zhang
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Jin
authors.forename: Jin-Jiao
authors.initials: JJ
authors.lastname: Jiang
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Ren
authors.forename: Jun-Mei
authors.initials: JM
authors.lastname: Jiang
authors.forename: Cheng-Yong
authors.initials: CY
authors.lastname: Qin
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010654:Phenylbutyrates / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid