Proapoptotic activity of NAG-1 is cell type specific and not related to COX-2 expression.
Non-steroidal anti-inflammatory drugs (NSAIDs) activated gene (NAG-1) is a newly identified member of the transforming growth factor-beta (TGF-beta) superfamily. Members of the TGF-beta family are multifunctional growth factors, and the nature of their effects depends on the cellular context and cell type. NAG-1 has antitumorigenic and proapoptotic activities in colon and gastric cancer cells lacking endogenous cyclooxgenase-2 (COX-2) expression. In contrast, COX-2 overexpression is related to antiapoptotic activity. The purpose of this study is to evaluate the proapoptotic activity of NAG-1 according to COX-2 expression and cell type. NAG-1 cDNA was transfected in SNU668 cells with endogenous COX-2 expression, SNU601 cells with forced COX-2 expression and Hep3B hepatocellular carcinoma cells. SNU668 cells with ectopic expression of NAG-1 showed markedly elevated subG1 population, induced death receptor-4 (DR-4) and DR-5, and revealed smaller active fragments of caspase-3. Forced COX-2 expression in SNU601 cells did not inhibit apoptosis caused by NAG-1 expression. Sulindac sulfide caused apoptosis, and induced expression of DR-5 and NAG-1 in Hep3B cells. However, Hep3B cells ectopically expressing NAG-1 did not cause apoptosis, and smaller active fragments of caspase-3 and an 85 kDa band of poly ADP-ribose polymerase (PARP) did not appear in the transfected cells, either. This study suggests that proapoptotic activity of NAG-1 is cell type specific and not related to COX-2 expression.
Jang
Tae Jung
TJ
Department of Pathology, Dongguk University College of Medicine, Suek-jang Dong 707, Kyongju, Kyongbuk 780-714, Korea. taejung@mail.dongguk.ac.kr
Kim
Nam Ii
NI
Lee
Chang Hun
CH
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D016193:G1 Phase / Q000187:drug effects; D055436:Growth Differentiation Factor 15; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013467:Sulindac / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection
D000970:Antineoplastic Agents; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D008565:Membrane Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; D013467:Sulindac; C025462:sulindac sulfide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases