Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, South Xiang-An Road, Xiamen, 361102, China.
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.
Amino Acids. 2020 May;52(5):793-809. doi: 10.1007/s00726-020-02853-0. Epub 2020 May 19.
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.
甘氨酸在快速增殖的癌细胞（如 A549 细胞）中发挥着关键作用。靶向甘氨酸代谢被认为是癌症治疗的一种潜在手段。然而，药物诱导的甘氨酸代谢变化尚未得到研究。在此，共检测了 34 种甘氨酸代谢物在有或没有抗癌药物治疗的 A549 细胞中的变化。这项工作表明，所有测试的抗癌药物都可以改变 A549 细胞中的甘氨酸代谢，包括抑制丙酮酸代谢和下调甜菜醛和 5'-磷酸核糖基甘氨酰胺。主成分分析和正交偏最小二乘判别分析显示了对照组和每个药物处理组之间的差异。一般来说，与阿法替尼、吉非替尼和他拉替尼相比，顺铂、喜树碱和 SAHA 可诱导更多代谢物的显著下调。甘氨酸、丝氨酸和苏氨酸代谢以及嘌呤代谢均受到阿法替尼、吉非替尼和他拉替尼的显著干扰。然而，顺铂、喜树碱和 SAHA 的治疗被认为是甘氨酸、丝氨酸和苏氨酸代谢以及半胱氨酸和蛋氨酸代谢紊乱的主要原因。最后，对对照组和所有药物处理组的多元分析显示有 11 种代谢物发生了显著变化。这意味着作用机制不同的抗癌药物可能会引起甘氨酸代谢组学的不同综合变化。本研究为了解抗癌药物在抑制癌细胞增殖的同时在甘氨酸代谢中的作用提供了基础，并可能有助于开发靶向甘氨酸代谢的癌症治疗方法。
