title: Anticancer effects of sodium butyrate on hepatocellular carcinoma cells in vitro.
abstract: In the present study, we investigated the anticancer effects of sodium butyrate (NaBu) on hepatocellular carcinoma (HCC) cells in vitro. As a histone deacetylase (HDAC) inhibitor, NaBu upregulated Ac-H3 and inhibited HDAC4 protein expression in a time- and dose-dependent manner. MTT assays showed that treatment with NaBu at high concentrations significantly inhibited the growth of various HCC cells. Exposure to NaBu for 24 h induced cell cycle arrest in the SMMC-7721 and HepG2 cells. NaBu also induced the apoptosis of SMMC‑7721 cells. The expression levels of cell cycle- and apoptosis-related proteins were further investigated by western blot analysis using specific antibodies. The results provided a possible mechanism responsible for the inhibitory effects of NaBu on the growth of HCC cells. To further analyze the role of NaBu in cell migration, wound healing and Transwell assays were performed, indicating that NaBu significantly inhibits cell migration/invasion in HCC cells. Transforming growth factor-β1 (TGF-β1)-induced epithelial to mesenchymal transition (EMT) has been associated with tumor cell migration and invasion. The EMT markers, E-cadherin, vimentin and N-cadherin, were regulated by TGF-β1, while NaBu inhibited this process in which HDAC4 and matrix metalloproteinase (MMP)7 may be involved. Based on our findings, we propose that NaBu may be useful as an anticancer drug for HCC therapy.
authors: Institute of Digestive Endoscopy and Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, PR China.
authors: Hong-Gang
authors: HG
authors: Wang
authors: Xiao-Dan
authors: XD
authors: Huang
authors: Peng
authors: P
authors: Shen
authors: Lu-Rong
authors: LR
authors: Li
authors: Hui-Ting
authors: HT
authors: Xue
authors: Guo-Zhong
authors: GZ
authors: Ji
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020148:Butyric Acid / Q000737:chemistry / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002453:Cell Cycle / Q000187:drug effects; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D056945:Hep G2 Cells; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms; D012097:Repressor Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D012097:Repressor Proteins; D053773:Transforming Growth Factor beta1; D020148:Butyric Acid; C400300:HDAC4 protein, human; D006655:Histone Deacetylases