title: The non-competitive metabotropic glutamate receptor-1 antagonist CPCCOEt inhibits the in vitro growth of human melanoma.
abstract: Five decades ago, the dicarboxylic amino acid glutamate became recognized as the major excitatory neurotransmitter in the central nervous system. In recent years, the expression of glutamate receptors was detected also in peripheral, non-neuronal tissues. Furthermore, it was found that glutamate stimulated the proliferation and migration of several peripheral tumor cells, and that glutamate receptor antagonists limited tumor growth. Most of these studies, however, used broad spectrum compounds and/or group-specific antagonists. Here we report that a selective, non-competitive metabotropic glutamate receptor-1 antagonist, CPCCOEt (7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester), significantly inhibited the proliferation and modified the morphology of two human melanoma cell lines. These effects were independent of the external glutamate level in the culture medium. In addition, CPCCOEt significantly enhanced the tumoricidal effects of cytostatic drugs. Thus, selective non-competitive metabotropic glutamate receptor antagonists may be used alone and/or with the synergistic effects of chemotherapy, thus enhancing existing therapies of melanoma and possibly other malignancies.
authors.affiliation: Department of Pathophysiology, Center of Molecular Medicine, Medical University Graz, 8010 Graz, Austria. helga.haas@meduni-graz.at
authors.forename: Helga Susanne
authors.initials: HS
authors.lastname: Haas
authors.forename: Roswitha
authors.initials: R
authors.lastname: Pfragner
authors.forename: Veronika
authors.initials: V
authors.lastname: Siegl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ingolic
authors.forename: Elfgard
authors.initials: E
authors.lastname: Heintz
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schraml
authors.forename: Konrad
authors.initials: K
authors.lastname: Schauenstein
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000648:ultrastructure; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D043823:Taxoids / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D000970:Antineoplastic Agents; D002867:Chromones; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D043823:Taxoids; D000077143:Docetaxel; D018698:Glutamic Acid