Curcumol simultaneously induces both apoptosis and autophagy in human nasopharyngeal carcinoma cells
Curcumol simultaneously induces both apoptosis and autophagy in human nasopharyngeal carcinoma cells
复制标题
姜黄酚同时诱导人鼻咽癌细胞凋亡和自噬。
DOI：
10.1002/ptr.7321
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发表时间：
2021-11-08
影响因子：
7.2
通讯作者：
Chen, Xu
中科院分区：
文献类型：
--
作者：
Wang, Juan;Liu, Guoxiang;Chen, Xu
自噬通常被认为是一种对抗细胞死亡的保护机制，同时也导致细胞损伤甚至凋亡。细胞凋亡和自噬的关系非常密切，在天然化合物引发的细胞死亡的进行性发生过程中，它们可能相互合作、共存或拮抗。因此，两种死亡模式之间的相互作用对癌细胞的整体命运至关重要。我们前期的研究发现莪术醇可诱导鼻咽癌细胞凋亡。最近，莪术醇被发现在癌细胞中诱导自噬。然而，莪术醇能否诱导鼻咽癌细胞自噬以及自噬对细胞凋亡的影响尚不清楚。在本研究中，我们发现莪术醇通过AMPK/mTOR通路诱导CNE-2细胞自噬。此外，自噬抑制剂3-甲基腺嘌呤（3-MA）或细胞凋亡抑制剂z-VAD-favorite抑制自噬显着增加增殖，而衰减的细胞凋亡和自噬与莪术醇212 μ M组相比。相反，将莪术醇与自噬激动剂雷帕霉素和凋亡诱导剂MG 132组合可协同莪术醇的凋亡和自噬作用。综上所述，我们的研究表明莪术醇通过AMPK/mTOR途径促进NPC细胞的自噬，诱导自噬增强莪术醇在NPC细胞中的活性，自噬诱导剂和莪术醇的联合应用可能成为NPC治疗的新策略。
Autophagy is usually considered as a protective mechanism against cell death, and in the meantime, leads to cell injury even apoptosis. Apoptosis and autophagy are very closely connected and may cooperate, coexist, or antagonize each other on progressive occurrence of cell death triggered by natural compounds. Therefore, the interplay between the two modes of death is essential for the overall fate of cancer cells. Our previous study revealed that curcumol induced apoptosis in nasopharyngeal carcinoma (NPC) cells. Recently, curcumol was found to induce autophagy in cancer cells. However, whether curcumol can induce NPC cells autophagy and the effects of autophagy on apoptosis remain elusive. In this study, we found that curcumol induced autophagy through AMPK/mTOR pathway in CNE-2 cells. Moreover, inhibiting autophagy by autophagy inhibitor 3-methyladenine (3-MA) or apoptosis inhibitor z-VAD-fmk significantly increased proliferation while attenuated apoptosis and autophagy compared with the curcumol 212 mu M group. In contrast, combining curcumol with autophagy agonist rapamycin and apoptosis inducer MG132 synergized the apoptotic and autophagic effect of curcumol. Taken together, our study demonstrates that curcumol promotes autophagy in NPC via AMPK/mTOR pathway, induces autophagy enhances the activity of curcumol in NPC cells; the combination of autophagy inducer and curcumol can be a new therapeutic strategy for NPC.