CASP3 and leukemia: In leukemia cell lines (Jurkat, HL60, K562, and U937), TSA has been shown to induce apoptosis through multiple mechanisms, including the up-regulation of DR4, DR5, Bax, Bak, Bim, PUMA, and Noxa, down-regulation of Mcl-1, Bcl-XL, Bcl-2, and cFLIP, the release of mitochondrial proteins (cytochrome c), induction of p21WAF1/CIP1 and p27KIP1, and activation of caspase-3 (38).