A Fas-associated death domain protein-dependent mechanism mediates the apoptotic action of non-steroidal anti-inflammatory drugs in the human leukemic Jurkat cell line.
Non-steroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase-1 and -2 and are useful for prevention and cure of cancers, especially colon and rectal cancers. The NSAIDs indomethacin and sulindac sulfide have been shown to induce apoptosis of colon epithelial cancer cells by a Bax-dependent mechanism that involves mitochondria-mediated activation of a caspase-9-dependent pathway. In this report, we demonstrate that indomethacin and sulindac sulfide induce apoptosis of human leukemic Jurkat cells by a mechanism that requires the Fas-associated Death Domain Protein-mediated activation of a caspase-8-dependent pathway. Therefore, NSAIDs induce apoptosis by different mechanisms depending on the cell type.
Han
Z
Z
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
Pantazis
P
P
Wyche
J H
JH
Kouttab
N
N
Kidd
V J
VJ
Hendrickson
E A
EA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis; D029681:Arabidopsis Proteins; D015153:Blotting, Western; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D013467:Sulindac / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D029681:Arabidopsis Proteins; C494826:BAX protein, human; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007527:Isoenzymes; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D013467:Sulindac; C025462:sulindac sulfide; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D007213:Indomethacin