title: Caspase-8 is scarcely silenced and its activity is well correlated with the anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand in gastric cancer cells.
abstract: The main apoptotic signal stimulated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) streams through caspase-8 activation and evokes caspase-3, a central apoptosis activator. In this study, the status of caspase-8 and -3 in gastric cancer cells related to the anticancer effects of TRAIL was investigated. In the caspase-8 gene promoter, 9 of 10 gastric cancer cell lines harbor no hypermethylation. The pretreatment amounts of caspase-8 and -3 in these cells were not predictors for the anticancer effect of TRAIL. Caspase-8 activity 24 h after treatment with TRAIL was well correlated with the anticancer effect of TRAIL (r=0.777, p=0.0060). Caspase-3 activity 24 h after treatment with TRAIL showed a trend towards an association with the anticancer effect of TRAIL (r=0.544, p=0.1067). These results suggested that gastric cancer might be a good target of TRAIL therapy because the majority of tumor cells have intact caspase-8 expression. The anticancer efficacy may be predicted by the degree of caspase-8 activation after TRAIL treatment.
authors.affiliation: Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kanehara
authors.forename: Bunzo
authors.initials: B
authors.lastname: Nakata
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases