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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Disruption of GRM1-mediated signalling using riluzole results in DNA damage in melanoma cells.

Authors: Wall, Brian A; Wangari-Talbot, Janet; Shin, Seung S; Schiff, Devora; Sierra, Jairo; Yu, Lumeng J; Khan, Atif; Haffty, Bruce; Goydos, James S; Chen, Suzie

Published In Pigment Cell Melanoma Res, (2014 Mar)

Abstract: Gain 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 of GRM1 is involved in the pathogenesis of certain human melanomas. Sustained stimulation of Grm1 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 and DNA damage response markers.

PubMed ID: 24330389 Exiting the NIEHS site

MeSH Terms: Acetylcysteine/pharmacology; Apoptosis/drug effects; Biopsy; Cell Line, Tumor; DNA Breaks, Double-Stranded/drug effects; DNA Damage*; Gene Knockdown Techniques; Glutamic Acid/metabolism; Glutathione/metabolism; Histones/metabolism; Humans; Intracellular Space/drug effects; Intracellular Space/metabolism; Melanoma/drug therapy; Melanoma/metabolism*; Melanoma/pathology*; Oxidative Stress/drug effects; Reactive Oxygen Species/metabolism; Receptors, Metabotropic Glutamate/metabolism*; Riluzole/pharmacology*; Riluzole/therapeutic use; Signal Transduction/drug effects*

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