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Open AccessArticle

2-Deoxy-d-Glucose-Induced Metabolic Alteration in Human Oral Squamous SCC15 Cells: Involvement of N-Glycosylation of Axl and Met

by Naeun Lee 1,†, Won-Jun Jang 1,†, Ji Hae Seo 2, Sooyeun Lee 1,* and Chul-Ho Jeong 1,*
1
College of Pharmacy, Keimyung University, Daegu 42601, Korea
2
Department of Biochemistry, Keimyung University School of Medicine, Daegu 42601, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Metabolites 2019, 9(9), 188; https://doi.org/10.3390/metabo9090188
Received: 23 August 2019 / Revised: 7 September 2019 / Accepted: 12 September 2019 / Published: 17 September 2019
(This article belongs to the Special Issue Metabolomics 2019)
One of the most prominent hallmarks of cancer cells is their dependency on the glycolytic pathway for energy production. As a potent inhibitor of glycolysis, 2-deoxy-d-glucose (2DG) has been proposed for cancer treatment and extensively investigated in clinical studies. Moreover, 2DG has been reported to interfere with other biological processes including glycosylation. To further understand the overall effect of and metabolic alteration by 2DG, we performed biochemical and metabolomics analyses on oral squamous cell carcinoma cell lines. In this study, we found that 2DG more effectively reduced glucose consumption and lactate level in SCC15 cells than in SCC4 cells, which are less dependent on glycolysis. Coincidentally, 2DG impaired N-linked glycosylation of the key oncogenic receptors Axl and Met in SCC15 cells, thereby reducing the cell viability and colony formation ability. The impaired processes of glycolysis and N-linked glycosylation were restored by exogenous addition of pyruvate and mannose, respectively. Additionally, our targeted metabolomics analysis revealed significant alterations in the metabolites, including amino acids, biogenic amines, glycerophospholipids, and sphingolipids, caused by the impairment of glycolysis and N-linked glycosylation. These observations suggest that alterations of these metabolites may be responsible for the phenotypic and metabolic changes in SCC15 cells induced by 2DG. Moreover, our data suggest that N-linked glycosylation of Axl and Met may contribute to the maintenance of cancer properties in SCC15 cells. Further studies are needed to elucidate the roles of these altered metabolites to provide novel therapeutic targets for treating human oral cancer. View Full-Text
Keywords: glycolysis; N-linked glycosylation; 2-deoxy-d-glucose; oral cancer; cancer metabolism glycolysis; N-linked glycosylation; 2-deoxy-d-glucose; oral cancer; cancer metabolism
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Lee, N.; Jang, W.-J.; Seo, J.H.; Lee, S.; Jeong, C.-H. 2-Deoxy-d-Glucose-Induced Metabolic Alteration in Human Oral Squamous SCC15 Cells: Involvement of N-Glycosylation of Axl and Met. Metabolites 2019, 9, 188.

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