JNK TNF CHX.pdfVIP

International Immunopharmacology 17 (2013) 92–98 Contents lists available at SciVerse ScienceDirect International Immunopharmacology j ourna l homepage: www.e lsev ie r .com/ locate / in t impJNK activation is required for TNFα-induced apoptosis in human hepatocarcinoma cellsValerio Giacomo Minero a,b, Amina Khadjavi a,c, Paola Costelli a,d, Francesco Maria Baccino a,d, Gabriella Bonelli a,d,? a Department of Experimental Medicine and Oncology, University of Turin, Italy b Department of Molecular Biotechnology and Health Sciences, University of Turin, Italy c Department of Oncology, University of Turin, Italy d Department of Clinical and Biological Sciences, University of Turin, Italy? Corresponding author at: University of Turin, Departm and Oncology, Corso Raffaello, 30, 10125 Turin, Italy. Te 0116707753. E-mail address: gabriella.bonelli@unito.it (G. Bonelli 1567-5769/$ – see front matter ? 2013 Elsevier B.V. All /10.1016/imp.2013.05.017a b s t r a c ta r t i c l e i n f oArticle history: Received 14 March 2013 Received in revised form 22 April 2013 Accepted 20 May 2013 Available online 7 June 2013 Keywords: TNF JNK Apoptosis Hepatocarcinoma Caspases Background: A frequent distinctive feature of tumors, hepatocellular carcinomas included, is resistance to ap- optosis induced by a variety of agents, among which the pleiotropic cytokine tumor necrosis factor-α (TNF). Compared to other cell types, hepatocytes and hepatoma-derived cell lines are poorly susceptible to TNF-induced apoptosis, which is largely ascribed to activation of the prosurvival transcription factor NF-κB and can be overcome by associating TNF to low doses of protein synthesis inhibitors or other drugs. Aims: This study analyses the molecular mechanisms by which TNF, in combination with cycloheximide (CHX), induces apoptosis in human hepatoma-derived Huh7 cells, focusing on the role played by JNK. Methods: Huh7 cell cultures were treated with TNF + CHX in the presence or in the absence of the panca