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基于生物测定引导分级分离和质谱分析的莱氏细胞毒性化合物对肺癌A549细胞系的代谢物谱分析。

Biological Assay-Guided Fractionation and Mass Spectrometry-Based Metabolite Profiling of L. Cytotoxic Compounds against Lung Cancer A549 Cell Line.

作者信息

Salac Edcyl Lee O, Alvarez Michael Russelle, Gaurana Rnie Shayne, Grijaldo Sheryl Joyce B, Serrano Luster Mae, Juan Florence de, Abogado Rowell, Padolina Isagani, Deniega Froila Marie, Delica Kimberly, Fernandez Kimberly, Lebrilla Carlito B, Manalo Marlon N, Heralde Iii Francisco M, Completo Gladys Cherisse J, Nacario Ruel C

机构信息

College of Arts and Sciences, University of the Philippines Visayas, Iloilo 5023, Philippines.

Institute of Chemistry, University of the Philippines Los Baños, Laguna 4031, Philippines.

出版信息

Plants (Basel). 2022 Sep 12;11(18):2380. doi: 10.3390/plants11182380.

DOI:10.3390/plants11182380
PMID:36145779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9503541/
Abstract

L. (Guyabano) leaves are reported to exhibit anticancer activity against cancer cells. In this study, the ethyl acetate extract from guyabano leaves was purified through column chromatography, and the cytotoxic effects of the semi-purified fractions were evaluated against A549 lung cancer cells using in vitro MTS cytotoxicity and scratch/wound healing assays. Fractions F15-16C and F15-16D exhibited the highest anticancer activity in the MTS assay, with % cytotoxicity values of 99.6% and 99.4%, respectively. The bioactivity of the fractions was also consistent with the results of the scratch/wound healing assay. Moreover, untargeted metabolomics was employed on the semi-purified fractions to determine the putative compounds responsible for the bioactivity. The active fractions were processed using LC-MS/MS analysis with the integration of the following metabolomic tools: MS-DIAL (for data processing), MetaboAnalyst (for data analysis), GNPS (for metabolite annotation), and Cytoscape (for network visualization). Results revealed that the putative compounds with a significant difference between active and inactive fractions in PCA and OPLS-DA models were pheophorbide A and diphenylcyclopropenone.

摘要

据报道,刺果番荔枝(番荔枝)叶对癌细胞具有抗癌活性。在本研究中,刺果番荔枝叶的乙酸乙酯提取物通过柱色谱法进行纯化,并使用体外MTS细胞毒性和划痕/伤口愈合试验评估半纯化级分对A549肺癌细胞的细胞毒性作用。F15 - 16C和F15 - 16D级分在MTS试验中表现出最高的抗癌活性,细胞毒性百分比值分别为99.6%和99.4%。这些级分的生物活性也与划痕/伤口愈合试验的结果一致。此外,对这些半纯化级分进行了非靶向代谢组学分析,以确定具有生物活性的推定化合物。使用LC - MS/MS分析结合以下代谢组学工具对活性级分进行处理:MS - DIAL(用于数据处理)、MetaboAnalyst(用于数据分析)、GNPS(用于代谢物注释)和Cytoscape(用于网络可视化)。结果显示,在主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS - DA)模型中,活性和非活性级分之间存在显著差异的推定化合物是脱镁叶绿酸A和二苯基环丙烯酮。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/8aadecd7a1fd/plants-11-02380-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/04223fad10d8/plants-11-02380-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/b7b717325679/plants-11-02380-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/832efca46e69/plants-11-02380-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/c64848bcc3af/plants-11-02380-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/8aadecd7a1fd/plants-11-02380-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/04223fad10d8/plants-11-02380-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/b7b717325679/plants-11-02380-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/832efca46e69/plants-11-02380-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/c64848bcc3af/plants-11-02380-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3910/9503541/8aadecd7a1fd/plants-11-02380-g005.jpg

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