title: Gene expression profiles of NO- and HNO-donor treated breast cancer cells: insights into tumor response and resistance pathways.
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 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.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: robert.cheng2@nih.gov.
authors.forename: Robert Y S
authors.initials: RY
authors.lastname: Cheng
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA; Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Debashree
authors.initials: D
authors.lastname: Basudhar
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Ridnour
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Julie L
authors.initials: JL
authors.lastname: Heinecke
authors.affiliation: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Aparna H
authors.initials: AH
authors.lastname: Kesarwala
authors.affiliation: Prostate Cancer Institute, NUI Galway, Ireland.
authors.forename: Sharon
authors.initials: S
authors.lastname: Glynn
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Switzer
authors.affiliation: Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ambs
authors.affiliation: Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Miranda
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Wink
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase
keywords: Breast cancer; Cancer biology; Cell signaling; Nitric oxide; Nitric oxide synthase; Nitroxyl