Han Z, Pantazis P, Wyche J H, Kouttab N, Kidd V J, Hendrickson E A
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
J Biol Chem. 2001 Oct 19;276(42):38748-54. doi: 10.1074/jbc.M106214200. Epub 2001 Aug 20.
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.
非甾体抗炎药（NSAIDs）是环氧化酶-1和-2的抑制剂，对癌症尤其是结肠癌和直肠癌的预防和治疗有用。NSAIDs吲哚美辛和舒林酸硫化物已被证明通过一种涉及线粒体介导的半胱天冬酶-9依赖性途径激活的Bax依赖性机制诱导结肠上皮癌细胞凋亡。在本报告中，我们证明吲哚美辛和舒林酸硫化物通过一种需要Fas相关死亡结构域蛋白介导的半胱天冬酶-8依赖性途径激活的机制诱导人白血病Jurkat细胞凋亡。因此，NSAIDs根据细胞类型通过不同机制诱导凋亡。
