Hypothetical model of 2-ME and HDACI interactions in human leukemia cells. In this model, combined exposure to HDACIs and 2-ME results in down-regulation/inactivation of antioxidant enzymes such as MnSOD, Trx, and GPx1, leading in turn to generation of free radicals, particularly O2 ^{· -} and H₂0₂. These events trigger, through an as-yet—to-be-determined mechanism, down-regulation of Akt, which induces activation of the stress-related kinase JNK. Sustained activation of JNK culminates in Bax translocation, cytochrome c release, activation of the caspase cascade, and apoptosis.