Grupo de Investigación Fitoquímica Universidad Javeriana (GIFUJ), Department of Chemistry, Faculty of Sciences, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.
Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE), Institute of Chemistry, São Paulo State University (UNESP), Araraquara 14800-900, Brazil.
Molecules. 2024 Jun 23;29(13):2985. doi: 10.3390/molecules29132985.
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 (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 (H-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.
代谢改变越来越被认为是结直肠癌（CRC）的重要方面，为鉴定治疗靶点提供了潜在途径。先前的研究已经证明了从（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，这些肿瘤细胞中改变的代谢途径尚不清楚。因此，本研究旨在采用非靶向代谢组学方法揭示 HCT-116 细胞暴露于 BLEGI 处理后内代谢组和外代谢组的代谢改变。首先，通过液相色谱-质谱联用（LC-MS）对 BLEGI 进行了化学特征分析。接下来，我们通过 MTT 评估了细胞活力，并通过针对结肠癌细胞的免疫荧光分析评估了形态学，通过 LPS 刺激的巨噬细胞模型评估了抗炎活性。随后，我们采用 LC-MS 和质子核磁共振（H-NMR）来研究细胞内和细胞外的变化。化学特征分析主要揭示了存在具有黄酮糖苷支架的化合物。免疫荧光分析显示染色质浓缩，随后形成凋亡小体，表明细胞通过凋亡死亡。代谢组学分析的结果显示了 98 种差异代谢物，涉及谷胱甘肽、三羧酸循环和硫辛酸代谢等。此外，BLEGI 在巨噬细胞中显示出显著的一氧化氮（NO）抑制能力。本研究加深了我们对 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。
