JS-K, a nitric oxide prodrug, induces cytochrome c release and caspase activation in HL-60 myeloid leukemia cells.
Nitric oxide (NO) induces differentiation and apoptosis in acute myelogenous leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent antileukemic activity. JS-K induces apoptosis in HL-60 cells by a caspase-dependent mechanism. The purpose of this study was to determine the pathway through which JS-K induces apoptosis. We show that JS-K alters mitochondrial membrane potential (DeltaPsim) and induces cytochrome c release from mitochondria into the cytoplasm. Treatment with JS-K resulted in activation of Caspase (Casp) 9, Casp 3 and Casp 8. JS-K constitutes a promising lead for a new class of anti-leukemic agents.
Udupi
Vidya
V
Medical Oncology, University of Utah, Salt Lake City, UT, USA.
Yu
Margaret
M
Malaviya
Swati
S
Saavedra
Joseph E
JE
Shami
Paul J
PJ
D017209:Apoptosis / Q000187:drug effects*; D001391:Azo Compounds / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism*; D045304:Cytochromes c / Q000032:analysis; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*
D001391:Azo Compounds; D020030:Nitric Oxide Donors; C474958:O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate; D010879:Piperazines; D045304:Cytochromes c; D020169:Caspases