Transglutaminase 2 expression levels regulate sensitivity to cystamine plus TRAIL-mediated apoptosis.
In this study, we demonstrate for the first time that cystamine, an inhibitor of transglutaminase 2 (TG2), enhanced tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in Caki cells, but not in normal human mesangial cells. Cystamine plus TRAIL-induced down-regulation of c-FLIP was recovered to basal levels by addition of the pancaspase inhibitor, z-VAD. The forced expression of c-FLIP attenuated cystamine plus TRAIL-mediated apoptosis in Caki cells. Although, cells expressing high levels of TG2 were more sensitive to cystamine plus TRAIL-mediated apoptosis than were cells expressing low levels of TG2, cystamine plus TRAIL-mediated apoptosis in the cell line expressing high levels of TG2 was reduced when TG2 levels were knocked down with siRNA. These results indicate that the level of TG2 modulates cystamine plus TRAIL-induced apoptosis. Taken together, the present findings suggest that cystamine may be an effective sensitizer of TRAIL-induced apoptosis in cancer cells expressing high levels of TG2.
Jang
Ji Hoon
JH
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.
Park
Jun Soo
JS
Lee
Tae-Jin
TJ
Kwon
Taeg Kyu
TK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D003538:Cystamine / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D034622:RNA Interference; D011994:Recombinant Proteins / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014162:Transfection; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020169:Caspases; D019204:GTP-Binding Proteins; D003538:Cystamine