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Updated: May 10, 2026

Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds
Published on: February 16, 2022
Nitric Oxide-Releasing Hybrid Drugs Target Cellular Processes Through S-Nitrosylation
1Department of Physiology, Pharmacology and Neuroscience, City University of New York Medical School, 138th Street and Convent Avenue, New York, NY 10031; Tel.: (212) 650-6641; -7692.
Abstract:
Nitric oxide (NO)-releasing agents such as JS-K and NO-releasing hybrids such as NO- and NONO-nonsteroidal anti-inflammatory drugs are novel agents with great potential for controlling cancer. Although studied extensively, a key question pertaining to their molecular targets and mechanism of action remains unclear: the role of NO in the overall biological effect of these agents. It has been shown that NO can directly modify sulfhydryl residues of proteins through S-nitrosylation and induce apoptosis. We showed that 3 structurally diverse NO-nonsteroidal anti-inflammatory drugs S-nitrosylated nuclear factor-κB p65 in vitro and in vivo and also showed that these agents S-nitrosylated caspase-3 in vivo. JS-K reduced nuclear β-catenin and cyclin D1 protein levels without affecting cytosolic β-catenin expression. On the basis of a time course study, S-nitrsolyation of nuclear β-catenin was determined to precede its degradation. These data provide a mechanistic role for NO and a rationale for the chemopreventive effects of these novel agents.
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