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

  1. Author:
    Udupi, V.
    Yu, M.
    Malaviya, S.
    Saavedra, J. E.
    Shami, P. J.

  2. Author Address

    Univ Utah, Salt Lake City, UT 84112 USA. SAIC, Frederick, MD USA.;Shami, PJ, Huntsman Canc Inst, Suite 2100,2000 Circle Hope, Salt Lake City, UT 84112 USA.;p.shami@m.cc.utah.edu
    1. Year: 2006
    2. Date: Oct
  2. Journal: Leukemia Research
    1. 30
    2. 10
    3. Pages: 1279-1283
  4. Type of Article: Article
  5. ISSN: 0145-2126
  1. Abstract:

    Nitric oxide (NO) induces differentiation and apoptosis in acute myelogenous leukemia (AML) cells. The NO prodrug O-2-(2,4-dinitrophenyl)l-[(4-ethoxycarbonyl)piperazin-l-yl]diazen-l-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 (Delta psi(m)) 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. (c) 2005 Elsevier Ltd. All rights reserved.

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External Sources

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  2. DOI: 10.1016/j.leukres.2005.12.007
  3. View record in Web of Science®
  4. WOS: 000240816600012

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