Research papers: Prostate CancerCritical role of the c-JunNH2-terminal kinase and p38 mitogen-activated protein kinase pathways on sodium butyrate-induced apoptosis in DU145 human prostate cancer cellsCho, Sung-Daea; Ahn, Nam-Shika; Jung, Ji-Wona; Yang, Se-Rana; Park, Joon-Suka; Lee, Yong-Soona; Jo, Eun-Hyea; Hwang, Jae-Woonga; Lii, Junxuanb; Kang, Kyung-Suna Author Information aDepartment of Veterinary Public Health, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Korea bHormel Institute, University of Minnesota, Austin, Minnesota, USA Correspondence to Dr Yong-Soon Lee and Kyung-Sun Kang, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, San 56-1, Sillim 9-dong, Gwanak-gu, Seoul 151-742, Korea Tel: +0082 2 880 1270; fax: +0082 2 876 7610; e-mail: [email protected] or [email protected] Received 4 March 2005 Accepted 20 June 2005 European Journal of Cancer Prevention 15(1):p 57-63, February 2006. | DOI: 10.1097/01.cej.0000195704.05246.fc Buy Metrics Abstract Sodium butyrate (NaBu) is known to exhibit anti-cancer effects via the differentiation and apoptosis of various carcinoma cells. However, the mechanism by which NaBu induces apoptosis and the involvement of protein kinases during apoptosis is not completely understood. To investigate the underlying pathways, we performed cell culture experiments in androgen-independent human prostate cancer (DU145 cells) focusing on various protein kinases. NaBu causes concentration-dependent cell detachment and growth inhibition. Exposure of DU145 cells to NaBu for 24 h caused a strong apoptotic effect with 26% nuclear fragmentation and condensation. In addition, NaBu induced caspase-3 and poly-ADP ribose polymerase cleavage and up-regulation of bax, suggesting that mitochondrial damage is involved in NaBu-induced caspase-dependent apoptosis. Interestingly, NaBu stimulated p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) activation, but not extracellular signal-regulated kinase 1/2 activation during apoptosis. Furthermore, NaBu up-regulated total protein levels and phospho forms of MAPK kinase 3 (MKK3) and MAPK kinase 4 (MKK4) as the upstream kinases of p38 MAPK and JNK independently of oxidative stress. Taken together, it is suggested that NaBu can be a promising chemopreventive agent for prostate cancer and the p38 MAPK and JNK pathways have critical roles in NaBu-induced apoptosis in DU145 cells. © 2006 Lippincott Williams & Wilkins, Inc.