TY - JOUR
T1 - Gene expression profiles of NO- and HNO-donor treated breast cancer cells
T2 - Insights into tumor response and resistance pathways
AU - Cheng, Robert Y.S.
AU - Basudhar, Debashree
AU - Ridnour, Lisa A.
AU - Heinecke, Julie L.
AU - Kesarwala, Aparna H.
AU - Glynn, Sharon
AU - Switzer, Christopher H.
AU - Ambs, Stefan
AU - Miranda, Katrina M.
AU - Wink, David A.
N1 - Publisher Copyright:
© Published by Elsevier Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Cancer biology
KW - Cell signaling
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Nitroxyl
UR - http://www.scopus.com/inward/record.url?scp=84913588785&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84913588785&partnerID=8YFLogxK
U2 - 10.1016/j.niox.2014.08.003
DO - 10.1016/j.niox.2014.08.003
M3 - Article
C2 - 25153034
AN - SCOPUS:84913588785
SN - 1089-8603
VL - 43
SP - 17
EP - 28
JO - Nitric Oxide - Biology and Chemistry
JF - Nitric Oxide - Biology and Chemistry
ER -