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.