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Glycine metabolomic changes induced by anticancer agents in A549 cells

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Abstract

Glycine plays a key role in rapidly proliferating cancer cells such as A549 cells. Targeting glycine metabolism is considered as a potential means for cancer treatment. However, the drug-induced alterations in glycine metabolism have not yet been investigated. Herein, a total of 34 glycine metabolites were examined in A549 cells with or without anticancer drug treatment. This work showed all tested anticancer agents could alter glycine metabolism in A549 cells including inhibition of pyruvate metabolism and down-regulation of betaine aldehyde and 5′-phosphoribosylglycinamide. Principal component analysis and orthogonal partial least-squares discrimination analysis exhibited the difference between control and each drug-treated group. In general, cisplatin, camptothecin, and SAHA could induce the significant down-regulation of more metabolites, compared with afatinib, gefitinib, and targretin. Both glycine, serine and threonine metabolism, and purine metabolism were significantly disturbed by the treatment with afatinib, gefitinib, and targretin. However, the treatment using cisplatin, camptothecin, and SAHA was considered to be highly responsible for the perturbation of glycine, serine and threonine metabolism, and cysteine and methionine metabolism. Finally, multivariate analysis for control and all drug-treated groups revealed 11 altered metabolites with a significant difference. It implies anti-cancer agents with different mechanisms of action might induce different comprehensive changes of glycine metabolomics. The current study provides fundamental insights into the acquisition of the role of anti-cancer agents in glycine metabolism while suppressing cancer cell proliferation, and may aid the development of cancer treatment targeting glycine metabolism.

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Acknowledgements

We thank the editor for careful review.

Funding

This work was supported by the National Natural Science Foundation of China (No. 81302652, 81773600, and 4187602), the Natural Science Foundation of Fujian Province of China (No. 2018J01132), and the Fundamental Research Funds for the Central Universities (No. 20720180051).

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  1. Kaiqiang Guo and Yin Cao have contributed equally to this paper.

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  1. Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China

    Kaiqiang Guo, Yin Cao, Zan Li, Xiaoxiao Zhou, Rong Ding, Kejing Chen, Yingkun Qiu, Zhen Wu & Meijuan Fang

  2. Department of Chemical Biology and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, Fujian, China

    Yan Liu

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  1. Kaiqiang Guo
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Contributions

YL, YKQ, ZW, and MJF conceived the study and participated in the research design. ZL, XXZ, YC, and KJC conducted the experiments. YC, KQG, and RD performed data analysis and (or) prepared the figures. YC, KQG, and MJF contributed to the writing of the manuscript. All of the authors discussed the complete dataset to establish an integral and coherent analysis.

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Correspondence to Zhen Wu or Meijuan Fang.

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Guo, K., Cao, Y., Li, Z. et al. Glycine metabolomic changes induced by anticancer agents in A549 cells. Amino Acids 52, 793–809 (2020). https://doi.org/10.1007/s00726-020-02853-0

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