Disruption ofGRM1‐mediated signalling using riluzole results inDNAdamage in melanoma cells

• DOI: 10.1111/pcmr.12207
• Publication Date: 2013-12-11T18:08:57Z
• Authors: Brian A. Wall; Janet Wangari‐Talbot; Seung S. Shin; Devora Schiff; Jairo Sierra; Lumeng J. Yu; Atif Khan; Bruce Haffty; James S. Goydos; Suzie Chen
• Keywords: 0301 basic medicine; Riluzole; Biopsy; Intracellular Space; Glutamic Acid; Apoptosis; Receptors, Metabotropic Glutamate; Glutathione; Acetylcysteine; Histones; Oxidative Stress; 03 medical and health sciences; Cell Line, Tumor; Gene Knockdown Techniques; Humans; DNA Breaks, Double-Stranded; Reactive Oxygen Species; Melanoma; DNA Damage; Signal Transduction

SummaryGain of function of the neuronal receptor, metabotropic glutamate receptor 1 (Grm1), was sufficient to induce melanocytic transformation in vitro and spontaneous melanoma development in vivo when ectopically expressed in melanocytes. The human form of this receptor,GRM1, has been shown to be ectopically expressed in a subset of human melanomas but not benign nevi or normal melanocytes, suggesting that misregulation ofGRM1 is involved in the pathogenesis of certain human melanomas. Sustained stimulation ofGrm1 by the ligand, glutamate, is required for the maintenance of transformed phenotypes in vitro and tumorigenicity in vivo. In this study, we investigate the mechanism of an inhibitor of glutamate release, riluzole, on human melanoma cells that express metabotropic glutamate receptor 1 (GRM1). Various in vitro assays conducted show that inhibition of glutamate release in several human melanoma cell lines resulted in an increase of oxidative stress andDNAdamage response markers.