Cannabinoid receptors as novel targets for the treatment of melanoma
Cannabinoid receptors as novel targets for the treatment of melanoma
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DOI：
10.1096/fj.06-6638fje
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发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Guzman, Manuel
中科院分区：
文献类型：
--
作者：
Blazquez, Cristina;Carracedo, Arkaitz;Guzman, Manuel
黑色素瘤是世界上导致皮肤癌相关死亡人数最多的疾病。尽管进行了深入的研究，预防和早期发现是对抗黑色素瘤的唯一有效措施，因此需要新的治疗策略来管理这种毁灭性疾病。在这里，我们评估了大麻素受体激动剂，一个新的家族潜在的抗肿瘤化合物，在皮肤黑色素瘤的疗效。人类黑色素瘤和黑色素瘤细胞系表达CB1和CB2大麻素受体。激活这些受体可减少小鼠黑色素瘤的生长、增殖、血管生成和转移，并增加细胞凋亡。大麻素抗黑素瘤活性独立于动物的免疫状态，可以在没有明显的精神活性作用的情况下实现，并且对黑色素瘤细胞与正常黑色素细胞具有选择性。大麻素对黑色素瘤细胞的抗增殖作用至少部分是由于通过抑制促存活蛋白Akt和低磷酸化的pRb视网膜母细胞瘤蛋白肿瘤抑制因子，在G1-S过渡阶段阻滞细胞周期。这些发现可能有助于设计新的化疗策略来管理黑色素瘤。
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.