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.

中文翻译：

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抗癌剂在A549细胞中诱导的甘氨酸代谢组学变化。

甘氨酸在迅速增殖的癌细胞如A549细胞中起关键作用。靶向甘氨酸代谢被认为是癌症治疗的潜在手段。但是，尚未研究药物诱导的甘氨酸代谢改变。在此，在有或没有抗癌药治疗的A549细胞中共检查了34种甘氨酸代谢产物。这项工作表明，所有测试过的抗癌剂均可以改变A549细胞中的甘氨酸代谢，包括抑制丙酮酸代谢以及下调甜菜碱醛和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对照组和每个药物治疗组之间的差异。一般而言，顺铂，喜树碱和SAHA可以诱导更多代谢物的显着下调，与afatinib，gefitinib和targretin比较。阿法替尼，吉非替尼和塔格列汀治疗严重干扰了甘氨酸，丝氨酸和苏氨酸的代谢以及嘌呤的代谢。然而，使用顺铂，喜树碱和SAHA的治疗被认为是导致甘氨酸，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治疗组进行多变量分析，发现11种代谢物发生了变化，差异有统计学意义。这意味着具有不同作用机理的抗癌药可能诱导甘氨酸代谢组学发生不同的全面变化。当前的研究为获得抗癌剂在甘氨酸代谢中的作用，同时抑制癌细胞的增殖提供了基本见解，