Document Detail

Growth inhibition and gene induction in human hepatocellular carcinoma cell exposed to sodium 4-phenylbutanoate.
MedLine Citation:
PMID:  19024104     Owner:  NLM     Status:  MEDLINE    
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.
Chun-Ting Wang; Mei Meng; Ji-Cheng Zhang; Chang-Jun Jin; Jin-Jiao Jiang; Hong-Sheng Ren; Jun-Mei Jiang; Cheng-Yong Qin; Dong-Qing Yu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chinese medical journal     Volume:  121     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-11-21     Completed Date:  2008-12-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  1707-11     Citation Subset:  IM    
Department of Medical Intensive Care Unit, Shandong Province Hospital, Affiliated Hospital of Shandong University, Jinan, Shandong 250021, China.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Blotting, Western
Cadherins / analysis
Carcinoma, Hepatocellular / drug therapy*,  metabolism,  pathology
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin-Dependent Kinase Inhibitor p21 / analysis
Enzyme Inhibitors / pharmacology*
Histone Deacetylase Inhibitors*
Liver Neoplasms / drug therapy*,  metabolism,  pathology
Phenylbutyrates / pharmacology*
Reg. No./Substance:
0/Antineoplastic Agents; 0/CDKN1A protein, human; 0/Cadherins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Enzyme Inhibitors; 0/Histone Deacetylase Inhibitors; 0/Phenylbutyrates; 1821-12-1/4-phenylbutyric acid

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