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Moreover, the \u03b2<jats:sub>2<\/jats:sub>m\u2010induced release of cytochrome c and AIF from the mitochondria in CCRF\u2010HSB\u20102 cells was caspase\u2010independent, since Z\u2010VAD\u2010fmk, a general inhibitor of caspases, did not block the release of these factors. However, Z\u2010VAD\u2010fmk treatment significantly blocked \u03b2<jats:sub>2<\/jats:sub>m\u2010induced apoptosis, while Western blot analysis revealed that caspases\u20101, \u20102, \u20103, \u20106, \u20107, \u20108 and \u20109 are not activated during \u03b2<jats:sub>2<\/jats:sub>m\u2010induced apoptosis in these cells. These results collectively indicate that a post\u2010mitochondrial caspase\u2010dependent mechanism is involved in \u03b2<jats:sub>2<\/jats:sub>m\u2010induced apoptosis. Moreover, \u03b2<jats:sub>2<\/jats:sub>m significantly enhanced the production of reactive oxygen species (ROS) during 12\u201348 hr treatment, and \u03b2<jats:sub>2<\/jats:sub>m\u2010induced apoptosis was almost totally inhibited in cells pre\u2010treated with the antioxidant N\u2010acetylcysteine (NAC), providing evidence that \u03b2<jats:sub>2<\/jats:sub>m\u2010induced apoptosis in CCRF\u2010HSB\u20102 cells is ROS\u2010dependent. Therefore, these results reveal that \u03b2<jats:sub>2<\/jats:sub>m\u2010induced apoptosis in CCRF\u2010HSB\u20102 cells may occur through an unknown caspase\u2010dependent and ROS\u2010dependent mechanism(s) that is associated with cytochrome c and AIF release from mitochondria, but is independent of the caspase \u20103, \u20108 and \u20109 pathways. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.10828","type":"journal-article","created":{"date-parts":[[2002,12,9]],"date-time":"2002-12-09T13:47:10Z","timestamp":1039441630000},"page":"316-327","source":"Crossref","is-referenced-by-count":39,"title":["\u03b2<sub>2<\/sub>\u2010microglobulin induces caspase\u2010dependent apoptosis in the CCRF\u2010HSB\u20102 human leukemia cell line independently of the caspase\u20103, \u20108 and \u20109 pathways but through increased reactive oxygen 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