Anti-tumoral action of cannabinoids:: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation
Anti-tumoral action of cannabinoids:: Involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation
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DOI：
10.1038/73171
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发表时间：
2000-03-01
期刊：
影响因子：
82.9
通讯作者：
Guzmán, M
中科院分区：
文献类型：
--
作者：
Galve-Roperh, I;Sánchez, C;Guzmán, M
δ（9）-四氢大麻酚是大麻的主要活性成分，可诱导培养中转化的神经细胞凋亡。在这里，我们表明，肿瘤内施用Delta（9）-四氢大麻酚和合成大麻素激动剂WIN-55，212 -2诱导Wistar大鼠和重组激活基因2缺陷小鼠的恶性胶质瘤显著消退。在所用条件下，大麻素治疗未产生任何实质性神经毒性作用。两个亚克隆的C6神经胶质瘤细胞培养的实验表明，大麻素信号凋亡的途径涉及大麻素受体，持续的神经酰胺积累和Raf 1/细胞外信号调节激酶激活。这些结果可能为恶性胶质瘤的治疗提供新的治疗方法。
Delta(9)-Tetrahydrocannabinol, the main active component of marijuana, induces apoptosis of transformed neural cells in culture. Here, we show that intratumoral administration of Delta(9)-tetrahydrocannabinol and the synthetic cannabinoid agonist WIN-55,212-2 induced a considerable regression of malignant gliomas in Wistar rats and in mice deficient in recombination activating gene 2. Cannabinoid treatment did not produce any substantial neurotoxic effect in the conditions used. Experiments with two subclones of C6 glioma cells in culture showed that cannabinoids signal apoptosis by a pathway involving cannabinoid receptors, sustained ceramide accumulation and Raf1/extracellular signal-regulated kinase activation. These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.