John Evans Professor, Chemistry; Judd A. and Marjorie Weinberg College of Arts and Sciences
Cancer and Physical Sciences
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Dr. Silverman's group synthesizes selective neuronal nitric oxide synthase (nNOS) inhibitors. Recently, a group at the University of California, Irvine, with which he collaborates, found that nNOS is present in melanocytes, a cell type that originates from the neural crest. In vitro studies demonstrated abundant expression of nNOS in melanoma compared to melanocytes, which is inducible by UV radiation and associated with increased NO generation. nNOS is also detected in biopsies of melanoma that increases with disease stage. Knockdown of nNOS in melanoma cells diminished L-arginine-induced NO production; the metastatic capacity was also reduced by the down regulations of MMP-1, Bcl-2, JunD, and APE/Ref-1. Similar inhibitions of NO and invasion potential were observed utilizing novel, highly selective nNOS inhibitors from the Silverman group. In 3-dimensional skin reconstruct, a nNOS inhibitor effectively reversed the overgrowth of melanoma stimulated by NO stress.