The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells
The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor cells
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DOI：
10.1016/j.ccr.2006.03.005
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发表时间：
2006-04-01
期刊：
影响因子：
50.3
通讯作者：
Velasco, G
中科院分区：
文献类型：
--
作者：
Carracedo, A;Lorente, M;Velasco, G
目前大麻素领域最令人兴奋的研究领域之一是研究这些化合物作为抗肿瘤药物的潜在应用。在这里，我们描述了介导大麻素诱导的肿瘤细胞凋亡的信号通路。通过使用广泛的实验方法，我们确定了压力调节蛋白p8（也被指定为转移1的候选者）作为大麻素抗肿瘤作用的重要介质，并表明p8上调依赖于从头合成的神经酰胺。我们还观察到p8通过上调内质网应激相关基因ATF-4、CHOP和TRB 3介导其凋亡作用。该途径的激活可能构成抑制肿瘤生长的潜在治疗策略。
One of the most exciting areas of current research in the cannabinoid field is the study of the potential application of these compounds as antitumoral drugs. Here, we describe the signaling pathway that mediates cannabinoid-induced apoptosis of tumor cells. By using a wide array of experimental approaches, we identify the stress-regulated protein p8 (also designated as candidate of metastasis 1) as an essential mediator of cannabinoid antitumoral action and show that p8 upregulation is dependent on de novo-synthesized ceramide. We also observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway may constitute a potential therapeutic strategy for inhibiting tumor growth.