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 Fesenkova, Charlotte A. Hanson, Joan L. Cmarik, Joseph E. Saavedra, Larry K. Keefer, Sandra K. Ruscetti

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

Fingerprint

Leukemia, Erythroblastic, Acute
Prodrugs
Nitric Oxide
Neoplasms
Mitogen-Activated Protein Kinase Kinases
Caspases
Phosphatidylinositol 3-Kinases
Apoptosis
Cell Line
Research

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Kaczmarek, M. Z., Holland, R. J., Lavanier, S. A., Troxler, J. A., Fesenkova, V., Hanson, C. A., ... 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

Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells. / Kaczmarek, Monika Z.; Holland, Ryan J.; Lavanier, Stephen A.; Troxler, Jami A.; Fesenkova, Valentyna; Hanson, Charlotte A.; Cmarik, Joan L.; Saavedra, Joseph E.; Keefer, Larry K.; Ruscetti, Sandra K.

In: Leukemia Research, Vol. 38, No. 3, 01.03.2014, p. 377-382.

Research output: Contribution to journalArticle

Kaczmarek, MZ, Holland, RJ, Lavanier, SA, Troxler, JA, Fesenkova, V, Hanson, CA, Cmarik, JL, Saavedra, JE, Keefer, LK & Ruscetti, SK 2014, 'Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells', Leukemia Research, vol. 38, no. 3, pp. 377-382. https://doi.org/10.1016/j.leukres.2013.12.002
Kaczmarek, Monika Z. ; Holland, Ryan J. ; Lavanier, Stephen A. ; Troxler, Jami A. ; Fesenkova, Valentyna ; Hanson, Charlotte A. ; Cmarik, Joan L. ; Saavedra, Joseph E. ; Keefer, Larry K. ; Ruscetti, Sandra K. / Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells. In: Leukemia Research. 2014 ; Vol. 38, No. 3. pp. 377-382.
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