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Gene expression profiles of no- and hno-donor treated breast cancer cells: insights into tumor response and resistance pathways

Cheng, Robert Y.S.
; 
Basudhar, Debashree
; 
Ridnour, Lisa A.
; 
Heinecke, Julie L.
; 
Kesarwala, Aparna H.
; 
Glynn, Sharon
; 
Switzer, Christopher H.
; 
Ambs, Stefan
; 
Miranda, Katrina M.
; 
Wink, David A.
Repository DOI
Publication Date
2014-12-01
Keywords
nitric oxide, nitroxyl, nitric oxide synthase, breast cancer, cell signaling, cancer biology, nitric-oxide synthase, reticulum stress pathway, nf-kappa-b, induced apoptosis, in-vivo, colorectal-cancer, colon-cancer, cardiovascular-system, murine macrophages, biological-systems
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Article
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Cheng, Robert Y.S. Basudhar, Debashree; Ridnour, Lisa A.; Heinecke, Julie L.; Kesarwala, Aparna H.; Glynn, Sharon; Switzer, Christopher H.; Ambs, Stefan; Miranda, Katrina M.; Wink, David A. (2014). Gene expression profiles of no- and hno-donor treated breast cancer cells: insights into tumor response and resistance pathways. Nitric Oxide 43 , 17-28
Abstract
Nitric oxide (NO) synthase 2 (NOS2), a major inflammatory protein, modulates disease progression via NO in a number of pathologies, including cancer. The role of NOS2-derived NO is not only flux-dependent, which is higher in mouse vs human cells, but also varies based on spatial and temporal distribution both within tumor cells and in the tumor microenvironment NO donors have been utilized to mimic NO flux conditions and to investigate the effects of varied NO concentrations. As a wide range of effects mediated by NO and other nitrogen oxides such as nitroxyl (HNO) have been elucidated, multiple NO- and HNO-releasing compounds have been developed as potential therapeutics, including as tumor modulators. One of the challenges is to determine differences in biomarker expression from extracellular vs intracellular generation of NO or HNO. Taking advantage of new NO and HNO releasing agents, we have characterized the gene expression profile of estrogen receptor-negative human breast cancer (MDA-MB-231) cells following exposure to aspirin, the NO donor DEA/NO, the HNO donor IPA/NO and their intracellularly-activated prodrug conjugates DEA/NO-aspirin and IPA/NO-aspirin. Comparison of the gene expression profiles demonstrated that several genes were uniquely expressed with respect to NO or HNO, such as miR-21, HSP70, cystathionine gamma-lyase and IL24. These findings provide insight into targets and pathways that could be therapeutically exploited by the redox related species NO and HNO. Published by Elsevier Inc.
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Publisher
Elsevier BV
Publisher DOI
10.1016/j.niox.2014.08.003
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)