The kinetics and redox state of nitric oxide determine the biological consequences in lung adenocarcinoma

Brandon G. Bentz, Neal D. Hammer, Brett Milash, Slobodanka Klein, David M. Burnett, James A. Radosevich, G. Kenneth Haines

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Few studies have explored the mechanistic basis for the apparent paradoxical effects of nitric oxide and its interrelated redox species (NO X) in cancer biology. Our aim was to determine the differential effects of the redox state and kinetics of nitrosative species on the key cancer processes of apoptosis. Therefore, a murine lung adenocarcinoma cell line was exposed to various NOX donor compounds differing in redox state and delivery kinetics. DNA strand breaks (DSBs) were measured by the alkaline single-cell gel electrophoresis assay (the COMET assay) and correlated with cell viability by the MTT and soft agar colony assays, while caspase enzymatic activity was measured using an in vitro fluorogenic caspase assay. Finally, cDNA microarrays defined apoptosis-related gene expression alterations resultant from these NOX donors. Exogenous NOX differentially influences DSBs, and apoptosis-related cell death and expression based on the redox state and kinetics of NOX delivery. In our murine lung adenocarcinoma model we have demonstrated differential effects of NOX based on the mode of delivery and redox state. These data suggest that the development of NOX-based cancer chemotherapy must consider the redox state and kinetics of delivery into their logical design.

Original languageEnglish
Pages (from-to)301-311
Number of pages11
JournalTumor Biology
Volume28
Issue number6
DOIs
StatePublished - Apr 2008
Externally publishedYes

Keywords

  • Apoptosis
  • Mutation
  • Nitric oxide
  • Tumor progression

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