Gene expression profiles of NO- and HNO-donor treated breast cancer cells: insights into tumor response and resistance pathways.

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 andtheir 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 γ-lyase and IL24. These findings provide insight into targets and pathways that could be therapeutically exploited by the redox related species NO and HNO.
AuthorsRobert Y S Cheng, Debashree Basudhar, Lisa A Ridnour, Julie L Heinecke, Aparna H Kesarwala, Sharon Glynn, Christopher H Switzer, Stefan Ambs, Katrina M Miranda, David A Wink
JournalNitric oxide : biology and chemistry / official journal of the Nitric Oxide Society (Nitric Oxide) Vol. 43 Pg. 17-28 (Dec 1 2014) ISSN: 1089-8611 [Electronic] United States
PMID25153034 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
CopyrightPublished by Elsevier Inc.
Chemical References
  • Nitric Oxide Donors
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Animals
  • Breast Neoplasms (genetics, therapy)
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm (drug effects)
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Mice
  • Nitric Oxide (pharmacology)
  • Nitric Oxide Donors (pharmacology)
  • Nitric Oxide Synthase (metabolism)
  • Signal Transduction

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