Glycine metabolomic changes induced by anticancer agents in A549 cells.

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.

• Authors: Kaiqiang Guo, Yin Cao, Zan Li, Xiaoxiao Zhou, Rong Ding, Kejing Chen, Yan Liu, Yingkun Qiu, Zhen Wu, Meijuan Fang
• Journal: Amino acids (Amino Acids) Vol. 52 Issue 5 Pg. 793-809 (May 2020) ISSN: 1438-2199 [Electronic] Austria
• PMID: 32430875 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Glycine

Topics

• A549 Cells
• Adenocarcinoma of Lung (drug therapy, metabolism, pathology)
• Antineoplastic Agents (pharmacology)
• Glycine (metabolism)
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Metabolic Networks and Pathways
• Metabolome (drug effects)