C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells
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 carcinom...
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MDPI AG
2014-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/15/2/3336 |
| _version_ | 1811201215404441600 |
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| author | Wenyuan Zhu Xinhua Wang Yi Zhou Huiming Wang |
| author_facet | Wenyuan Zhu Xinhua Wang Yi Zhou Huiming Wang |
| author_sort | Wenyuan Zhu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:17:13Z |
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| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T02:17:13Z |
| publishDate | 2014-02-01 |
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| spelling | doaj.art-e2ffb4cda7ae47588bedc23d974286c22022-12-22T03:52:13ZengMDPI AGInternational Journal of Molecular Sciences1422-00672014-02-011523336335510.3390/ijms15023336ijms15023336C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma CellsWenyuan Zhu0Xinhua Wang1Yi Zhou2Huiming Wang3Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, ChinaDepartment of Oral Implantology, the Affiliated Hospital of Stomatology, College of Medicine, Zhejiang University, Hangzhou 310003, ChinaDepartment of Oral Implantology, the Affiliated Hospital of Stomatology, College of Medicine, Zhejiang University, Hangzhou 310003, ChinaDepartment of Oral and Maxillofacial Surgery, the First Affiliated Hospital, Zhejiang University, Hangzhou 310003, ChinaCeramides 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.http://www.mdpi.com/1422-0067/15/2/3336head and neck squamous cell carcinomaC2-ceramideapoptosisnecroptosisautophagyERK1/2 pathway |
| spellingShingle | Wenyuan Zhu Xinhua Wang Yi Zhou Huiming Wang C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells International Journal of Molecular Sciences head and neck squamous cell carcinoma C2-ceramide apoptosis necroptosis autophagy ERK1/2 pathway |
| title | C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells |
| title_full | C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells |
| title_fullStr | C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells |
| title_full_unstemmed | C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells |
| title_short | C2-Ceramide Induces Cell Death and Protective Autophagy in Head and Neck Squamous Cell Carcinoma Cells |
| title_sort | c2 ceramide induces cell death and protective autophagy in head and neck squamous cell carcinoma cells |
| topic | head and neck squamous cell carcinoma C2-ceramide apoptosis necroptosis autophagy ERK1/2 pathway |
| url | http://www.mdpi.com/1422-0067/15/2/3336 |
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