Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells

Monika Z. Kaczmarek, Ryan J. Holland, Stephen A. Lavanier, Jami A. Troxler, Valentyna I. Fesenkova, Charlotte A. Hanson, Joan L. Cmarik, Joseph E. Saavedra, Larry K. Keefer, Sandra K. Ruscetti

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The nitric oxide (NO) prodrug JS-K, a promising anti-cancer agent, consists of a diazeniumdiolate group necessary for the release of NO as well as an arylating ring. In this study, we research the mechanism by which JS-K kills a murine erythroleukemia cell line and determine the roles of NO and arylation in the process. Our studies indicate that JS-K inhibits the PI 3-kinase/Akt and MAP kinase pathways. This correlates with the activation of the tumor suppressor FoxO3a and increased expression of various caspases, leading to apoptosis. The arylating capability of JS-K appears to be sufficient for inducing these biological effects. Overall, these data suggest that JS-K kills tumor cells by arylating and inactivating signaling molecules that block the activation of a tumor suppressor.

Original languageEnglish (US)
Pages (from-to)377-382
Number of pages6
JournalLeukemia Research
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2014

Keywords

  • Apoptosis
  • FoxO3a
  • JS-K
  • Murine erythroleukemia cells

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Kaczmarek, M. Z., Holland, R. J., Lavanier, S. A., Troxler, J. A., Fesenkova, V. I., Hanson, C. A., Cmarik, J. L., Saavedra, J. E., Keefer, L. K., & Ruscetti, S. K. (2014). Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells. Leukemia Research, 38(3), 377-382. https://doi.org/10.1016/j.leukres.2013.12.002