Research findings from University of Dusseldorf update understanding of apoptosis
2008 JAN 14 -- "Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not in most normal cells and has therefore been proposed as a promising antitumor agent. Recent experiments suggested that isolated primary human hepatocytes but not monkey liver cells are susceptible to certain TRAIL agonists, raising concerns about the use of TRAIL in cancer treatment," researchers in Dusseldorf, Germany report. "Whether TRAIL indeed exerts hepatotoxicity in vivo and how this is influenced by chemotherapeutic drugs or liver disease are completely unknown. Employing different forms of recombinant TRAIL, we found that the cytokine can induce proapoptotic caspase activity in isolated human hepatocytes. However in marked contrast, these different TRAIL preparations induced little or no cytotoxicity when incubated with tissue explants of fresh healthy liver, an experimental model that may more faithfully mimic the in vivo situation. In healthy liver, TRAIL induced apoptosis only when combined with histone deacetylase inhibitors. Strikingly, however, TRAIL alone triggered massive apoptosis accompanied by caspase activation in tissue explants from patients with liver steatosis or hepatitis C viral infection. This enhanced sensitivity of diseased liver was associated with an increased expression of TRAIL receptors and up-regulation of proapoptotic Bcl-2 proteins," wrote X. Volkmann and colleagues, University of Dusseldorf. The researchers concluded: "These results suggest that clinical trials should be performed with great caution when TRAIL is combined with chemotherapy or administered to patients with inflammatory liver diseases." Volkmann and colleagues published their study in Hepatology (Increased hepatotoxicity of tumor necrosis factor-related apoptosis-inducing ligand in diseased human liver. Hepatology, 2007;46(5):1498-1508). For additional information, contact X. Volkmann, University of Dusseldorf, Institute Molecular Medical, University of Str 1, D-40225 Dusseldorf, Germany. Publisher contact information for the journal Hepatology is: John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA. Keywords: Germany, Dusseldorf, Apoptosis, Cancer, Caspase, Enzyme Research, Gastroenterology, Hepatology, Liver Disease, Necrosis, Oncology, University of Dusseldorf. This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2008, Proteomics Weekly via NewsRx.com.
|
