Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma
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Zheng Wang1,*, Lijun Wen1,*, Fei Zhu1,*, Yanping Wang1, Qing Xie1, Zijun Chen2 and Yunsen Li1
1Institutes of Biology and Medical Sciences, Medical College, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
2Shanghai University of Traditional Chinese Medicine, Shanghai, China
*These authors have contributed equally to this work
Zijun Chen, email: [email protected]
Yunsen Li, email: [email protected]
Keywords: ceramide synthase 1; C18-ceramide; glioma; mass spectrometry; autophagy
Received: March 29, 2017 Accepted: September 25, 2017 Published: October 23, 2017
Ceramide synthase 1 (CERS1) is the most highly expressed CERS in the central nervous system, and ceramide with an 18-carbon–containing fatty acid chain (C18-ceramide) in the brain plays important roles in signaling and sphingolipid development. However, the roles of CERS1 and C18-ceramide in glioma are largely unknown. In the present study, measured by electrospray ionization linear ion trap mass spectrometry, C18-ceramide was significantly lower in glioma tumor tissues compared with controls (P < 0.001), indicating that C18-ceramide might have a role in glioma. These roles were examined by reconstitution of C18-ceramide in U251 and A172 glioma cells via addition of exogenous C18-ceramide or overexpression of CERS1, which has been shown to specifically induce the generation of C18-ceramide. Overexpression of CERS1 or adding exogenous C18-ceramide inhibited cell viability and induced cell death by activating endoplasmic reticulum stress, which induced lethal autophagy and inhibited PI3K/AKT signal pathway in U251 and A172 glioma cells. Moreover, overexpression of CERS1 or adding exogenous C18-ceramide increased the sensitivity of U251 and A172 glioma cells to teniposide (VM-26). Thus, the combined therapy of CERS1/C18-ceramide and VM-26 may be a novel therapeutic strategy for the treatment of human glioma.
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