关键词: Guadua incana HCT-116 cells anti-inflammatory activity bamboo leaf extract cytotoxic activity endometabolome exometabolome metabolomics

Mesh : Humans Plant Extracts / pharmacology chemistry Plant Leaves / chemistry Colonic Neoplasms / drug therapy metabolism pathology HCT116 Cells Metabolomics / methods Metabolome / drug effects Cell Survival / drug effects Apoptosis / drug effects Animals RAW 264.7 Cells Mice Chromatography, Liquid

来  源:   DOI:10.3390/molecules29132985   PDF(Pubmed)

Abstract:
Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI\'s possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.
摘要:
代谢改变越来越被认为是结直肠癌(CRC)的重要方面。为确定治疗靶点提供了潜在的途径。先前的研究已经证明了从Guaduaincana(BLEGI)获得的竹叶提取物对HCT-116结肠癌细胞的细胞毒性潜力。然而,这些肿瘤细胞中代谢途径的改变尚不清楚.因此,本研究旨在采用非靶向代谢组学方法来揭示HCT-116细胞在暴露于BLEGI治疗后代谢组和外代谢组的代谢改变.首先,BLEGI的化学表征通过液相色谱与质谱联用(LC-MS)进行。接下来,我们通过MTT和形态学分析对结肠癌细胞进行免疫荧光分析,和抗炎活性使用LPS刺激的巨噬细胞模型。随后,我们使用LC-MS和质子核磁共振(1H-NMR)来研究细胞内和细胞外变化。化学表征主要揭示了具有黄酮糖苷支架的化合物的存在。免疫荧光分析显示凝聚的染色质和随后的凋亡小体的形成,提示细胞凋亡死亡。代谢组学分析结果显示98种差异代谢物,参与谷胱甘肽,三羧酸循环,硫辛酸代谢,在其他人中。此外,BLEGI在巨噬细胞中表现出显著的一氧化氮(NO)抑制能力。这项研究增强了我们对BLEGI可能作用机制的理解,并为治疗这种疾病的治疗靶点提供了新的见解。
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