PubMed:12912965 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/12912965","sourcedb":"PubMed","sourceid":"12912965","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/12912965","text":"Role of antiapoptotic proteins in tumor necrosis factor-related apoptosis-inducing ligand and cisplatin-augmented apoptosis.\nPURPOSE AND EXPERIMENTAL DESIGN: The purpose of this study was to examine the effect of combined treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and cisplatin in human head and neck squamous cell carcinoma. HNSCC-6 cells were treated with 0.1-1 micro g/ml TRAIL and/or 1-10 micro g/ml cisplatin for 24 h.\nRESULTS: TRAIL alone or cisplatin alone caused minimal cytotoxicity. The combination of TRAIL and cisplatin synergistically enhanced apoptotic death, caspase-8 and caspase-3 activation, as well as poly(ADP-ribose) polymerase cleavage. However, the total cellular levels and the surface expression of TRAIL receptor proteins, such as death receptors 4 and 5 and decoy receptors 2 and 1, were not significantly changed by treatment with TRAIL and cisplatin. Interestingly, the level of the short form of Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (FLIP(S)) but not the long form of Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein was reduced through cleavage. Benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone a caspase-3 inhibitor, blocked the cleavage of FLIP(S) and caspase-3 activation. Overexpression of FLIP(S) protected cells from apoptotic death and FLIP(S) cleavage during treatment with TRAIL in combination with cisplatin.\nCONCLUSIONS: These results suggest that caspase-3 is responsible for FLIP(S) cleavage, and the cleavage of FLIP(S) is one of facilitating factors for TRAIL-induced apoptotic death.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":237,"end":258},"obj":"gene:7124"},{"id":"T1","span":{"begin":324,"end":361},"obj":"disease:C1168401"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"12912965-1#79#100#gene7124","span":{"begin":237,"end":258},"obj":"gene7124"},{"id":"12912965-1#166#203#diseaseC1168401","span":{"begin":324,"end":361},"obj":"diseaseC1168401"}],"relations":[{"id":"79#100#gene7124166#203#diseaseC1168401","pred":"associated_with","subj":"12912965-1#79#100#gene7124","obj":"12912965-1#166#203#diseaseC1168401"}],"attributes":[{"subj":"12912965-1#79#100#gene7124","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"12912965-1#166#203#diseaseC1168401","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":158,"end":460},"obj":"OBJECTIVE"},{"id":"T2","span":{"begin":470,"end":1480},"obj":"RESULTS"},{"id":"T3","span":{"begin":1494,"end":1661},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#93ec9b","default":true},{"id":"DisGeNET5_gene_disease","color":"#ec93a4"},{"id":"PubMed_Structured_Abstracts","color":"#93beec"}]}]}}