2. Academic Validation
  3. 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

  • Int J Mol Sci. 2014 Feb 21;15(2):3336-55. doi: 10.3390/ijms15023336.
Wenyuan Zhu 1,  Xinhua Wang 2,  Yi Zhou 3,  Huiming Wang 4
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China. [email protected].
  • 2 Department of Oral Implantology, the Affiliated Hospital of Stomatology, College of Medicine, Zhejiang University, Hangzhou 310003, China. [email protected].
  • 3 Department of Oral Implantology, the Affiliated Hospital of Stomatology, College of Medicine, Zhejiang University, Hangzhou 310003, China. [email protected].
  • 4 Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China. [email protected].
PMID: 24566153 DOI: 10.3390/ijms15023336
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.

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