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The Kinetics and Redox State of Nitric Oxide Determine the Biological Consequences in Lung Adenocarcinoma
- Source :
- Tumor Biology. 28:301-311
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 2007.
-
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 NO(X) 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 NO(X) donors. Exogenous NO(X) differentially influences DSBs, and apoptosis-related cell death and expression based on the redox state and kinetics of NO(X) delivery. In our murine lung adenocarcinoma model we have demonstrated differential effects of NO(X) based on the mode of delivery and redox state. These data suggest that the development of NO(X)-based cancer chemotherapy must consider the redox state and kinetics of delivery into their logical design.
- Subjects :
- Lung Neoplasms
Kinetics
Apoptosis
Adenocarcinoma
Biology
Nitric Oxide
Redox
Nitric oxide
Colony-Forming Units Assay
Mice
chemistry.chemical_compound
Biomarkers, Tumor
Tumor Cells, Cultured
medicine
Animals
Nitric Oxide Donors
RNA, Messenger
Cancer biology
Nitrites
NOx
Oligonucleotide Array Sequence Analysis
Mice, Inbred BALB C
Lung
Reverse Transcriptase Polymerase Chain Reaction
DNA, Neoplasm
General Medicine
medicine.disease
medicine.anatomical_structure
Biochemistry
chemistry
Caspases
Comet Assay
Oxidation-Reduction
DNA Damage
Subjects
Details
- ISSN :
- 14230380 and 10104283
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Tumor Biology
- Accession number :
- edsair.doi.dedup.....75e52ba43c07db6024195db1bb27fabc