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Int J Mol Sci. 2014 Feb 21;15(2):3336-55. doi: 10.3390/ijms15023336.

C2-ceramide induces cell death and protective autophagy in head and neck squamous cell carcinoma cells.

Author information

1
Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China. zwy555star@163.com.
2
Department of Oral Implantology, the Affiliated Hospital of Stomatology, College of Medicine, Zhejiang University, Hangzhou 310003, China. wxhalex@163.com.
3
Department of Oral Implantology, the Affiliated Hospital of Stomatology, College of Medicine, Zhejiang University, Hangzhou 310003, China. zhouyizyzyzy@163.com.
4
Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China. huimingw1960@hotmail.com.

Abstract

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.

PMID:
24566153
PMCID:
PMC3958915
DOI:
10.3390/ijms15023336
[Indexed for MEDLINE]
Free PMC Article
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