JS-K, a nitric oxide prodrug, induces cytochrome c release and caspase activation in HL-60 myeloid leukemia cells

Leuk Res. 2006 Oct;30(10):1279-83. doi: 10.1016/j.leukres.2005.12.007. Epub 2006 Jan 24.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Azo Compounds / pharmacology*
  • Caspases / metabolism*
  • Cytochromes c / analysis
  • HL-60 Cells
  • Humans
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / physiology
  • Nitric Oxide Donors / pharmacology*
  • Piperazines / pharmacology*

Substances

  • Azo Compounds
  • Nitric Oxide Donors
  • O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate
  • Piperazines
  • Cytochromes c
  • Caspases