| Literature DB >> 24461365 |
Monika Z Kaczmarek1, Ryan J Holland2, Stephen A Lavanier1, Jami A Troxler1, Valentyna I Fesenkova1, Charlotte A Hanson1, Joan L Cmarik1, Joseph E Saavedra3, Larry K Keefer2, Sandra K Ruscetti4.
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. Published by Elsevier Ltd.Entities:
Keywords: Apoptosis; FoxO3a; JS-K; Murine erythroleukemia cells
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Year: 2013 PMID： 24461365 PMCID： PMC3943942 DOI： 10.1016/j.leukres.2013.12.002
Source DB: PubMed Journal: Leuk Res ISSN： 0145-2126 Impact factor: 3.156