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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Authors | Wenyuan Zhu, Xinhua Wang, Yi Zhou, Huiming Wang |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 15
Issue 2
Pg. 3336-55
(Feb 21 2014)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 24566153
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- N-acetylsphingosine
- MTOR protein, human
- TOR Serine-Threonine Kinases
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Caspase 3
- Sphingosine
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Topics |
- Apoptosis
(drug effects)
- Autophagy
(drug effects)
- Carcinoma, Squamous Cell
(metabolism, pathology)
- Caspase 3
(metabolism)
- Cell Line, Tumor
- DNA Fragmentation
(drug effects)
- Head and Neck Neoplasms
(metabolism, pathology)
- Humans
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Necrosis
- Phosphorylation
(drug effects)
- Signal Transduction
(drug effects)
- Sphingosine
(analogs & derivatives, toxicity)
- TOR Serine-Threonine Kinases
(metabolism)
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