title: Induction of the Intrinsic Apoptotic Pathway by 3-Deazaadenosine Is Mediated by BAX Activation in HL-60 Cells.
abstract: 3-Deazaadenosine (DZA), a potent inhibitor of S-adenosylhomocysteine hydrolase, was previously proposed to induce intrinsic apoptosis in human leukemic cells. In the present study, we analyzed the mechanism underlying the DZA-induced intrinsic apoptotic pathway. DZA activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an accumulation of hypo-diploidic cells, the processing of multiple procaspases and an inhibitory effect of z-VAD-Fmk on this cell death. During DZA-induced apoptosis, cytochrome c (cyt c) was released into the cytosol. This was neither prevented by z-VAD-Fmk and nor was it associated with the dissipation of mitochondrial membrane potential (ΔΨ(m)). Prior to the release of cyt c, BAX was translocated from the cytosol to mitochondria and underwent oligomerization. Finally, the overexpression of BCL-XL protected HL-60 cells from apoptosis by blocking both the cyt c release and BAX oligomerization. Collectively, these findings suggest that DZA may activate intrinsic apoptosis by stimulating BAX activation and thereby the release of cyt c.
authors.affiliation: Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Kyoung-Won
authors.initials: KW
authors.lastname: Ko
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Kang
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Choe
authors.forename: Yoon-Hyoung
authors.initials: YH
authors.lastname: Kim
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Ho-Shik
authors.initials: HS
authors.lastname: Kim