title: Augmentation of sodium butyrate-induced apoptosis by p38 MAP kinase inhibition in rat liver epithelial cells.
abstract: Sodium butyrate (NaBu) has an inhibitory effect on histone deacetylases (HDACs). The mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAP, kinase are known to be modulated during NaBu-induced apoptosis. In the present study, we showed that low concentrations of NaBu could induce apoptosis synergistically with the inhibition of p38 MAP kinase as proven by using specific p38 MAP kinase inhibitor and dominant negative p38 transfection in a ras-transformed rat liver epithelial cell line (WB-ras). There were no changes in HDAC1, suggesting that NaBu might be able to kill transformed cells bypassing the HDAC inhibitory effect. We further demonstrated that inhibition of p38 MAP kinase potentiated apoptotic cascades, including cleavage of poly(ADP-ribose) polymerase, caspase-3, and decrease in Bcl-2/Bax ratio even at a lower concentration of NaBu. Thus, p38 MAP kinase played inhibitory roles in NaBu-induced apoptosis, and simultaneous modulation of MAP kinases in NaBu treatment could increase the efficiency of the chemotherapeutic effect of NaBu.
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Jung
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Nam-Shik
authors.initials: NS
authors.lastname: Ahn
authors.forename: Se-Ran
authors.initials: SR
authors.lastname: Yang
authors.forename: Joon-Suk
authors.initials: JS
authors.lastname: Park
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Jo
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Hwang
authors.forename: Okezie I
authors.initials: OI
authors.lastname: Aruoma
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Yong-Soon
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008099:Liver / Q000166:cytology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D002087:Butyrates; D004791:Enzyme Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases