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Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Proteome Res. 2020, 19, 2, 781-793
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1H NMR-Based Metabolic Profiles Delineate the Anticancer Effect of Vitamin C and Oxaliplatin on Hepatocellular Carcinoma Cells

  • Caigui Lin
    Caigui Lin
    Department of Electronic Science, Fujian Provincial Key Laboratory for Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian 361005, China
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  • , 
  • Jiyang Dong
    Jiyang Dong
    Department of Electronic Science, Fujian Provincial Key Laboratory for Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian 361005, China
    More by Jiyang Dong
    Orcidhttp://orcid.org/0000-0002-1064-6548
  • , 
  • Zhiliang Wei
    Zhiliang Wei
    Department of Radiology, Johns Hopkins University, Baltimore, Maryland 21205, United States
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  • , 
  • Kian-Kai Cheng
    Kian-Kai Cheng
    Innovation Centre in Agritechnology, Universiti Teknologi Malaysia, Muar, Johor 84600, Malaysia
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  • , 
  • Jie Li
    Jie Li
    Department of Hepatobiliary Surgery, ZhongShan Hospital of Xiamen University, Xiamen, Fujian 361005, China
    Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, ZhongShan Hospital of Xiamen University, Xiamen, Fujian 361005, China
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  • , 
  • Song You
    Song You
    Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, ZhongShan Hospital of Xiamen University, Xiamen, Fujian 361005, China
    Graduate College of Fujian Medical University, Fuzhou, Fujian 350004, China
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  • , 
  • Yueyue Liu
    Yueyue Liu
    Department of Electronic Science, Fujian Provincial Key Laboratory for Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian 361005, China
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  • , 
  • Xiaomin Wang*
    Xiaomin Wang
    Department of Hepatobiliary Surgery, ZhongShan Hospital of Xiamen University, Xiamen, Fujian 361005, China
    Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, ZhongShan Hospital of Xiamen University, Xiamen, Fujian 361005, China
    *E-mail: [email protected]. Phone: +86139-5010-2636. Fax: +86-592-2993131 (X.W.).
    More by Xiaomin Wang
  • , and 
  • Zhong Chen*
    Zhong Chen
    Department of Electronic Science, Fujian Provincial Key Laboratory for Plasma and Magnetic Resonance, Xiamen University, Xiamen, Fujian 361005, China
    *E-mail: [email protected]. Phone: +86189-5928-1712. Fax: +86-592-2181812 (Z.C.).
    More by Zhong Chen
    Orcidhttp://orcid.org/0000-0002-1473-2224
Cite this: J. Proteome Res. 2020, 19, 2, 781–793
Publication Date (Web):January 9, 2020
https://doi.org/10.1021/acs.jproteome.9b00635
Copyright © 2020 American Chemical Society
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    Abstract

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    Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Because of its high recurrence rate and heterogeneity, effective treatment for advanced stage of HCC is currently lacking. There are accumulating evidences showing the therapeutic potential of pharmacologic vitamin C (VC) on HCC. However, the metabolic basis underlying the anticancer property of VC remains to be elucidated. In this study, we used a high-resolution proton nuclear magnetic resonance-based metabolomics technique to assess the global metabolic changes in HCC cells following VC treatment. In addition, the HCC cells were also treated with oxaliplatin (OXA) to explore the potential synergistic effect induced by the combined VC and OXA treatment. The current metabolomics data suggested different mechanisms of OXA and VC in modulating cell growth and metabolism. In general, VC treatment led to inhibition of energy metabolism via NAD+ depletion and amino acid deprivation. On the other hand, OXA caused significant perturbation in phospholipid biosynthesis and phosphatidylcholine biosynthesis pathways. The current results highlighted glutathione metabolism, and pathways related to succinate and choline may play central roles in conferring the combined effect between OXA and VC. Taken together, this study provided metabolic evidence of VC and OXA in treating HCC and may contribute toward the potential application of combined VC and OXA as complementary HCC therapies.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jproteome.9b00635.

    • Workflow of MSEA, flowchart of metabolic pathway analysis, summary plot of QEA for comparisons between the OXA and SM groups, summary plot of QEA for comparisons between the VC and SM groups, summary plot of QEA for comparisons between the OXA + VC and SM groups, summary of the identified differential metabolites constructed from the comparison models, and summary of the QEA on identified differential metabolites (PDF)

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    Cited By

    This article is cited by 9 publications.

    1. Yongpei Wang, Xingxing Liu, Liheng Dong, Kian-Kai Cheng, Caigui Lin, Xiaomin Wang, Jiyang Dong, Lingli Deng, Daniel Raftery. iMSEA: A Novel Metabolite Set Enrichment Analysis Strategy to Decipher Drug Interactions. Analytical Chemistry 2023, 95 (15) , 6203-6211. https://doi.org/10.1021/acs.analchem.2c04603
    2. Daniela S. C. Bispo, Marlene Correia, Tatiana J. Carneiro, Ana S. Martins, Aliana A. N. Reis, Ana L. M. Batista de Carvalho, Maria P. M. Marques, Ana M. Gil. Impact of Conventional and Potential New Metal-Based Drugs on Lipid Metabolism in Osteosarcoma MG-63 Cells. International Journal of Molecular Sciences 2023, 24 (24) , 17556. https://doi.org/10.3390/ijms242417556
    3. Caigui Lin, Qing Hu, Jiyang Dong, Zhiliang Wei, Jie Li, Zhong Chen. Serum metabolic signatures of schizophrenia patients complicated with hepatitis B virus infection: A 1H NMR-based metabolomics study. Frontiers in Psychiatry 2022, 13 https://doi.org/10.3389/fpsyt.2022.998709
    4. Veronica Ghini, Francesca Magherini, Lara Massai, Luigi Messori, Paola Turano. Comparative NMR metabolomics of the responses of A2780 human ovarian cancer cells to clinically established Pt-based drugs. Dalton Transactions 2022, 51 (33) , 12512-12523. https://doi.org/10.1039/D2DT02068H
    5. Yangbo Xu, Yafei Li, Xiaofan Chen, Feifan Xiang, Yong Deng, Zhong Li, Daiqing Wei. TGF-β protects osteosarcoma cells from chemotherapeutic cytotoxicity in a SDH/HIF1α dependent manner. BMC Cancer 2021, 21 (1) https://doi.org/10.1186/s12885-021-08954-7
    6. Franziska Böttger, Andrea Vallés-Martí, Loraine Cahn, Connie R. Jimenez. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. Journal of Experimental & Clinical Cancer Research 2021, 40 (1) https://doi.org/10.1186/s13046-021-02134-y
    7. Ana S. Martins, Ana L. M. Batista de Carvalho, Maria P. M. Marques, Ana M. Gil. Response of Osteosarcoma Cell Metabolism to Platinum and Palladium Chelates as Potential New Drugs. Molecules 2021, 26 (16) , 4805. https://doi.org/10.3390/molecules26164805
    8. Paulo R. Ribeiro, Elisangela F. Boffo. NMR Approaches for Probing the Polar Metabolome. 2021, 185-218. https://doi.org/10.1039/9781839163524-00185
    9. Ganesan Raja, Youngmi Jung, Sang Hoon Jung, Tae-Jin Kim. 1H-NMR-based metabolomics for cancer targeting and metabolic engineering –A review. Process Biochemistry 2020, 99 , 112-122. https://doi.org/10.1016/j.procbio.2020.08.023
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