C2-ceramide induces cell death and protective autophagy in head and neck squamous cell carcinoma cells.
C2-ceramide induces cell death and protective autophagy in head and neck squamous cell carcinoma cells.
复制标题
C2-神经酰胺诱导头颈鳞状细胞癌细胞死亡和保护性自噬
DOI：
10.3390/ijms15023336
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发表时间：
2014-02-21
影响因子：
5.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhu W;Wang X;Zhou Y;Wang H
神经酰胺是参与癌细胞中的几种细胞内过程的第二信使。本研究的目的是通过研究头颈部鳞状细胞癌（HNSCC）细胞中的细胞死亡和自噬来评估C2-神经酰胺（C2-Cer; N-乙酰基-d-鞘氨醇）的抗肿瘤功效。C2-Cer对HN 4和HN 30细胞株的细胞毒作用呈浓度依赖性。同时诱导caspase-3非依赖性凋亡和程序性坏死。C2-Cer显著增加与保护性自噬相关的微管相关蛋白1轻链3B（LC 3B）II型的表达水平。自噬抑制剂增强C2-Cer介导的细胞毒性，而程序性坏死抑制剂产生相反的效果。此外，C2-Cer在自噬过程中上调细胞外信号调节激酶1/2的磷酸化，下调其下游底物磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）。这些结果表明，C2-Cer通过诱导HNSCC中的程序性凋亡和坏死来发挥抗肿瘤作用，并且这些细胞毒性作用被自噬抑制剂增强。
Ceramides are second messengers involved in several intracellular processes in cancer cells, amongst others. The aim of this study was to evaluate the anti-tumor efficacy of C2-ceramide (C2-Cer; N-acetyl-d-sphingosine) by investigating cell death and autophagy in head and neck squamous cell carcinoma (HNSCC) cells. C2-Cer showed concentration-dependent cytotoxicity in HN4 and HN30 cell lines. It simultaneously induced caspase-3-independent apoptosis and programmed necrosis. C2-Cer markedly increased the expression level of microtubule-associated protein 1 light chain 3B (LC3B) type II associated with protective autophagy. An autophagy inhibitor enhanced C2-Cer-mediated cytotoxicity, while a programmed-necrosis inhibitor produced the opposite effect. Furthermore, C2-Cer up-regulated the phosphorylation of extracellular signal-regulated kinase 1/2, but down-regulated its downstream substrate phospho-mammalian target of rapamycin (p-mTOR) during the autophagy process. These results suggested that C2-Cer exerts anti-tumor effects by inducing programmed apoptosis and necrosis in HNSCC, and these cytotoxic effects are enhanced by an autophagy inhibitor.
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DOI：
10.1016/j.radonc.2010.06.010
发表时间：
2010-11
期刊：
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
影响因子：
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作者：
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影响因子：
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DOI：
10.1016/j.bbalip.2013.09.005
发表时间：
2014-05
期刊：
Biochimica et biophysica acta
影响因子：
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影响因子：
5.8
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影响因子：
4.8
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