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高通量代谢组学揭示了野麦在癌细胞系中对疏水性代谢组的失调调控。

High-throughput metabolomics reveals dysregulation of hydrophobic metabolomes in cancer cell lines by Eleusine indica.

机构信息

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Jalan UMS, 88400, Kota Kinabalu, Sabah, Malaysia.

Biotechnology Research Institute, Universiti Malaysia Sabah, Jalan UMS, 88400, Kota Kinabalu, Sabah, Malaysia.

出版信息

Sci Rep. 2022 Jun 6;12(1):9347. doi: 10.1038/s41598-022-13575-6.

DOI:10.1038/s41598-022-13575-6
PMID:35668092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9168358/
Abstract

Eleusine indica, which is used in traditional medicine, exhibits antiproliferative activity against several cancer cell lines. However, metabolomic studies to evaluate the metabolite changes induced by E. indica in cancer cells are still lacking. The present study investigated the anticancer effects of a root fraction of E. indica (R-S5-C1-H1) on H1299, MCF-7, and SK-HEP-1 cell lines and analyzed metabolic changes in the treated cancer cells using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Cell metabolic activity assays demonstrated that the cell viability of the three cancer cell lines was significantly reduced following treatment with R-S5-C1-H1, with half-maximal inhibitory concentrations values of 12.95 µg/mL, 15.99 µg/mL, and 13.69 µg/mL at 72 h, respectively. Microscopy analysis using Hoechst 33342 and Annexin V fluorescent dyes revealed that cells treated with R-S5-C1-H1 underwent apoptotic cell death, while chemometric analysis suggested that apoptosis was triggered 48 h after treatment with R-S5-C1-H1. Deconvoluted cellular metabolomics revealed that hydrophobic metabolites were significantly altered, including triacylglycerols, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and ceramide, suggesting that apoptosis induction by R-S5-C1-H1 potentially occurred through modulation of phospholipid synthesis and sphingolipid metabolism. These metabolomic profiling results provide new insights into the anticancer mechanisms of E. indica and facilitate the overall understanding of molecular events following therapeutic interventions.

摘要

珍珠茅,一种传统药物,对几种癌细胞系表现出抗增殖活性。然而,评估珍珠茅在癌细胞中引起的代谢物变化的代谢组学研究仍然缺乏。本研究调查了珍珠茅根部分(R-S5-C1-H1)对 H1299、MCF-7 和 SK-HEP-1 细胞系的抗癌作用,并使用超高效液相色谱高分辨率质谱(UHPLC-HRMS)分析了处理后的癌细胞中的代谢变化。细胞代谢活性测定表明,三种癌细胞系的细胞活力在 R-S5-C1-H1 处理后显著降低,72 小时时的半最大抑制浓度值分别为 12.95μg/mL、15.99μg/mL 和 13.69μg/mL。使用 Hoechst 33342 和 Annexin V 荧光染料的显微镜分析表明,用 R-S5-C1-H1 处理的细胞发生了凋亡性细胞死亡,而化学计量学分析表明,R-S5-C1-H1 处理 48 小时后触发了细胞凋亡。去卷积细胞代谢组学显示,疏水性代谢物发生了显著变化,包括三酰甘油、磷脂酰胆碱、磷脂酰乙醇胺、神经鞘磷脂和神经酰胺,这表明 R-S5-C1-H1 诱导的细胞凋亡可能是通过调节磷脂合成和鞘脂代谢发生的。这些代谢组学分析结果为珍珠茅的抗癌机制提供了新的见解,并有助于全面了解治疗干预后的分子事件。

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