Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells
Metformin is a widely prescribed anti-diabetes drug with potential utilities for cancer therapies. Several studies have related metformin to the reduced risk of cholangiocarcinoma (CCA), highlighting its potentialities for the treatments of CCA. However, the underlying molecular mechanisms remain el...
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| Format: | Article |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.570516/full |
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| author | Jin Zhang Jin Zhang Caihua Hang Ting Jiang Shenghui Yi Wei Shao Wengang Li Donghai Lin |
| author_facet | Jin Zhang Jin Zhang Caihua Hang Ting Jiang Shenghui Yi Wei Shao Wengang Li Donghai Lin |
| author_sort | Jin Zhang |
| collection | DOAJ |
| description | Metformin is a widely prescribed anti-diabetes drug with potential utilities for cancer therapies. Several studies have related metformin to the reduced risk of cholangiocarcinoma (CCA), highlighting its potentialities for the treatments of CCA. However, the underlying molecular mechanisms remain elusive. Here, we demonstrated that metformin treatment could inhibit proliferations of the human CCA cell lines Mz-ChA-1 and QBC939 in dose-dependent manners. The NMR-based metabonomic analyses showed distinct discriminations between the metformin-treated (Met) and control (Ctrl) groups of both CCA cells. Characteristic metabolites were identified by a combination of multivariate statistical analysis of 1D 1H-NMR spectral data and the pair-wise t-test of metabolite levels. We then identified four significantly altered metabolic pathways based on the characteristic metabolites, including glucose metabolism, oxidative stress-related metabolism, energy metabolism, and amino acids metabolism. Comparing CCA cells with normal human umbilical vein endothelial cells (HUVECs), we found that metformin treatment profoundly promoted glycolysis and specifically increased the levels of BCAAs and UDP-GlcNAc, implying the occurrence of autophagy and cell cycle arrest in metformin-treated CAA cells. This work provides a mechanistic understanding of the anticancer effect of metformin treatment on CAA cells, and is beneficial to further developments of metformin as an anticancer drug. |
| first_indexed | 2024-12-22T19:43:58Z |
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| id | doaj.art-4d6073bb5e5c400cae348d6524e584e0 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T19:43:58Z |
| publishDate | 2020-11-01 |
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| series | Frontiers in Oncology |
| spelling | doaj.art-4d6073bb5e5c400cae348d6524e584e02022-12-21T18:14:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-11-011010.3389/fonc.2020.570516570516Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma CellsJin Zhang0Jin Zhang1Caihua Hang2Ting Jiang3Shenghui Yi4Wei Shao5Wengang Li6Donghai Lin7Department of Hepatobiliary Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaCollege of Chemistry and Chemical Engineering, Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen, ChinaDepartment of Physical Education, Xiamen University of Technology, Xiamen, ChinaCollege of Chemistry and Chemical Engineering, Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen, ChinaCollege of Chemistry and Chemical Engineering, Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen, ChinaAffiliated Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen, ChinaDepartment of Hepatobiliary Surgery, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaCollege of Chemistry and Chemical Engineering, Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen, ChinaMetformin is a widely prescribed anti-diabetes drug with potential utilities for cancer therapies. Several studies have related metformin to the reduced risk of cholangiocarcinoma (CCA), highlighting its potentialities for the treatments of CCA. However, the underlying molecular mechanisms remain elusive. Here, we demonstrated that metformin treatment could inhibit proliferations of the human CCA cell lines Mz-ChA-1 and QBC939 in dose-dependent manners. The NMR-based metabonomic analyses showed distinct discriminations between the metformin-treated (Met) and control (Ctrl) groups of both CCA cells. Characteristic metabolites were identified by a combination of multivariate statistical analysis of 1D 1H-NMR spectral data and the pair-wise t-test of metabolite levels. We then identified four significantly altered metabolic pathways based on the characteristic metabolites, including glucose metabolism, oxidative stress-related metabolism, energy metabolism, and amino acids metabolism. Comparing CCA cells with normal human umbilical vein endothelial cells (HUVECs), we found that metformin treatment profoundly promoted glycolysis and specifically increased the levels of BCAAs and UDP-GlcNAc, implying the occurrence of autophagy and cell cycle arrest in metformin-treated CAA cells. This work provides a mechanistic understanding of the anticancer effect of metformin treatment on CAA cells, and is beneficial to further developments of metformin as an anticancer drug.https://www.frontiersin.org/articles/10.3389/fonc.2020.570516/fullcholangiocarcinomametforminmetabolomicnuclear magnetic resonance (NMR)anticancer |
| spellingShingle | Jin Zhang Jin Zhang Caihua Hang Ting Jiang Shenghui Yi Wei Shao Wengang Li Donghai Lin Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells Frontiers in Oncology cholangiocarcinoma metformin metabolomic nuclear magnetic resonance (NMR) anticancer |
| title | Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells |
| title_full | Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells |
| title_fullStr | Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells |
| title_full_unstemmed | Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells |
| title_short | Nuclear Magnetic Resonance-Based Metabolomic Analysis of the Anticancer Effect of Metformin Treatment on Cholangiocarcinoma Cells |
| title_sort | nuclear magnetic resonance based metabolomic analysis of the anticancer effect of metformin treatment on cholangiocarcinoma cells |
| topic | cholangiocarcinoma metformin metabolomic nuclear magnetic resonance (NMR) anticancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.570516/full |
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