5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Adenoviral vector expressing CYLD augments antitumor activity of TRAIL by suppression of NF-kappaB survival signaling in hepatocellular carcinoma.

      Cancer Biology & Therapy

      Adenoviridae, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Survival, Genes, Tumor Suppressor, Genetic Vectors, Humans, Liver Neoplasms, NF-kappa B, antagonists & inhibitors, physiology, Signal Transduction, TNF-Related Apoptosis-Inducing Ligand, genetics, Tumor Suppressor Proteins

      Read this article at

      ScienceOpenPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          CYLD is a tumor suppressor gene related to cylindroma and is negative regulator of NF-kappaB. However, antitumor effect of CYLD has not been reported. The activation of NF-kappaB induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) renders hepatocellular carcinoma (HCC) resistant to TRAIL-mediated cell apoptosis. Here we described that the adenoviral vector expressing CYLD (Ad/hTERT-CYLD) augmented the cytotoxicity of TRAIL in HCC cells by negatively regulating NF-kappaB activity since CYLD could reverse the ubiquitination of TNF receptor-associated factor 2 (TRAF2) and interact with the IkappaB kinasegamma (IKKgamma). The combined treatment of Ad/hTERT-CYLD and a conditionally replicating adenovirus carrying TRAIL gene (ZD55-TRAIL) induced rapid and potent apoptosis in HCC cells, characterized by activation of caspase-3, caspase-8, PARP and the reduction of X-linked inhibitor of apoptosis protein (XIAP). In animal study, the combined treatment could eradicate the BEL7404 xenograft tumors. In contrast, treatment with Ad/hTERT-CYLD or ZD55-TRAIL alone achieved less antitumor effect. CYLD inhibits TRAIL-mediated NF-kappaB activation and enhances the sensitivity of HCC cells to TRAIL-triggered apoptosis. The combined delivery of Ad/hTERT-CYLD and ZD55-TRAIL may be a new useful strategy for HCC or other tumor cells with enhanced NF-kappaB activity.

          Related collections

          Author and article information

          Journal
          16627981

          Comments

          Comment on this article