TRAIL-induced apoptosis in type I leukemic cells is not enhanced by overexpression of Bax

We have previously shown that Bax translocation was crucial in TNF alpha or etoposide-induced apoptosis. Overexpression of Bax sensitized chronic myel oid leukemic K562 cells to etoposide-induced apoptosis, Treatment with TNF- related apoptosis-inducing ligand (TRAIL) induces a loss of mitochondrial m embrane potential (Delta Psim), cytochrome c release from mitochondria, act ivation of caspases-8, -9, and -3, and cleavage of Bid in the K562 cell Lin e. Bax failed to sensitize K562 cells to TRAIL-induced apoptosis. TRAIL did not induce Bax expression and/or translocation from cytosol to mitochondri a in the K562 cell line. However, 100 muM Z-VAD.fmk, a pan caspase inhibito r, completely blocked TRAIL-initiated mitochondrial alterations and cleavag es of caspases and Bid. We propose that TRAIL-induced apoptosis in K562 cel ls is via Type I apoptotic signal pathway. Bax translocation is not essenti al for TRAIL-induced cytochrome c release and Delta Psim collapse in the Ty pe I cells. (C) 2001 Academic Press.