The biphasic nature of nitric oxide responses in tumor biology.
The dual or biphasic responses of cancer to nitric oxide (NO) arise from its concentration dependent ability to regulate tumor growth, migration, invasion, survival, angiogenesis, and metastasis. The outcome of these various NO-dependent processes is dictated by several factors including NO flux, the chemical redox environment, and the duration of NO exposure. Further, it was recently discovered that an NO-induced redox flux in vascular endothelial cells hypersensitizes these cells to the antiangiogenic effects of thrombospondin-1. This suggests a novel treatment paradigm for targeting tumor-driven angiogenesis that combines redox modulation with mimetic derivatives of thrombospondin-1. This article discusses the biphasic nature of NO in cancer biology and the implications of NO-driven redox flux for modulation of tumor-stimulated angiogenesis, growth, and metastasis.
Ridnour
Lisa A
LA
Tumor Biology Section, Radiation Biology Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. ridnourl@mail.nih.gov
Thomas
Douglas D
DD
Donzelli
Sonia
S
Espey
Michael G
MG
Roberts
David D
DD
Wink
David A
DA
Isenberg
Jeffrey S
JS
D000818:Animals; D001695:Biology; D040761:Biomimetic Materials / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009569:Nitric Oxide / Q000494:pharmacology*; D010084:Oxidation-Reduction; D019700:Thrombospondin 1 / Q000494:pharmacology; D013997:Time Factors
D019700:Thrombospondin 1; D009569:Nitric Oxide