title: Adenovirus-mediated gene transfer of caspase-8 sensitizes human adenocarcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand.
abstract: Resistance to apoptosis has been implicated in the poor response of cancer cells to various anti-tumor agents. Caspase-8 is a family member of executioner caspases associated with tumor necrosis factor (TNF) family death receptors-mediated apoptotic signaling cascade. In this study, to specify caspase-8-mediated apoptotic activity, we examined the anti-tumor effect of adenoviral vector expressing caspase-8 (Adv-caspase-8) in combination with TNF-related apoptosis-inducing ligand (TRAIL) which induces specifically caspase-8 activation. First, we demonstrated that expression procaspase-8 is related to apoptosis sensitivity to TRAIL in pancreatic and colonic cancer cells. In human pancreatic cancer cell line Panc1 which demonstrates low expression of procaspase-8, Adv-caspase-8 transfection strongly augmented TRAIL-induced apoptosis. Adv-caspase-8 similarly enhanced the susceptibility of human colonic cancer cell line Colo320DM to TRAIL. These results suggest that Adv-caspase-8 may be a good combination partner of TRAIL and enables TRAIL to be a more potent anticancer agent in a wide range of adenocarcinoma cells which demonstrate low expression of caspase-8.
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA. hiroshi_yasui@dfci.harvard.edu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yasui
authors.forename: Masaaki
authors.initials: M
authors.lastname: Adachi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases