Antileukemic drugs increase death receptor 5 levels and enhance Apo-2L-induced apoptosis of human acute leukemia cells

摘要: In present studies, treatment with tumor necrosis factor (TNF)–related apoptosis inducing ligand (TRAIL, also known as Apo-2 [Apo-2L]) is shown to induce of the human acute leukemia HL-60, U937, and Jurkat cells in a dose-dependent manner, maximum effect seen following 0.25 μg/mL Apo-2L (95.0% ± 3.5% apoptotic cells). Susceptibility these cell types, which are lack p53wt function, did not appear correlate levels apoptosis-signaling death receptors (DRs) Apo-2L, ie, DR4 DR5; decoy (DcR1 2); FLAME-1 (cFLIP); or proteins inhibitors (IAP) family. Apo-2L–induced was associated processing caspase-8, Bid, cytosolic accumulation cytochrome c well caspase-9 caspase-3. significantly inhibited HL-60 that overexpressed Bcl-2 Bcl-xL. Cotreatment either caspase-8 inhibitor suppressed apoptosis. Treatment leukemic etoposide, Ara-C, doxorubicin increased DR5 but DR4, Fas, DcR1, DcR2, Fas ligand, levels. Importantly, sequential followed by induced more than doxorubicin, Ara-C alone, cotreatment antileukemic drugs, reverse sequence one drugs. These findings indicate up-regulates p53-independent manner sensitizes