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      Cannabinoid receptors as novel targets for the treatment of melanoma

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          Abstract

          Melanoma causes the greatest number of skin cancer-related deaths worldwide. Despite intensive research, prevention and early detection are the only effective measures against melanoma, so new therapeutic strategies are necessary for the management of this devastating disease. Here, we evaluated the efficacy of cannabinoid receptor agonists, a new family of potential antitumoral compounds, at skin melanoma. Human melanomas and melanoma cell lines express CB1 and CB2 cannabinoid receptors. Activation of these receptors decreased growth, proliferation, angiogenesis and metastasis, and increased apoptosis, of melanomas in mice. Cannabinoid antimelanoma activity was independent of the immune status of the animal, could be achieved without overt psychoactive effects and was selective for melanoma cells vs. normal melanocytes. Cannabinoid antiproliferative action on melanoma cells was due, at least in part, to cell cycle arrest at the G1-S transition via inhibition of the prosurvival protein Akt and hypophosphorylation of the pRb retinoblastoma protein tumor suppressor. These findings may contribute to the design of new chemotherapeutic strategies for the management of melanoma.

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          Most cited references 37

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          The molecular logic of endocannabinoid signalling.

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            Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors

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              Identification and functional characterization of brainstem cannabinoid CB2 receptors.

              The presence and function of CB2 receptors in central nervous system (CNS) neurons are controversial. We report the expression of CB2 receptor messenger RNA and protein localization on brainstem neurons. These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors. CB2 receptors represent an alternative site of action of endocannabinoids that opens the possibility of nonpsychotropic therapeutic interventions using enhanced endocannabinoid levels in localized brain areas.
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                Author and article information

                Journal
                The FASEB Journal
                The FASEB Journal
                FASEB
                0892-6638
                1530-6860
                December 2006
                December 2006
                : 20
                : 14
                : 2633-2635
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain;
                [2 ]Cell Division and Cancer Group, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; and
                [3 ]Unit of Molecular Genetics, Marqués de Valdecilla University Hospital, Santander, Spain
                Article
                10.1096/fj.06-6638fje
                17065222
                © 2006
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