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从根部分离出的诱导凋亡香豆素的评估：通过线粒体介导途径治疗白血病的潜力。

Evaluation of Apoptosis-Inducing Coumarins Isolated from Roots: The Potential for Leukemia Treatment via the Mitochondria-Mediated Pathway.

作者信息

Kang Kyung-Yun, Ramos Sonny C, Lee Sung-Ju, Nam Sang-Jip, Kim Jong-Jin

机构信息

R&D Team, Suncheon Research Center for Bio Health Care, Suncheon 57962, Republic of Korea.

Department of Biomedical Science, Sunchon National University, Suncheon 57922, Republic of Korea.

出版信息

Cells. 2024 Nov 29;13(23):1982. doi: 10.3390/cells13231982.

DOI:10.3390/cells13231982
PMID:39682730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11639758/
Abstract

Inducing programmed cell death in tumors is a fundamental approach in cancer therapy, prompting extensive efforts to discover bioactive compounds with anticancer properties. , a plant used in traditional medicine across East Asia, has been reported to exhibit various biological activities, including anticancer effects. This study aimed to evaluate the apoptosis-inducing effects of methanol/dichloromethane (MeOH/CHCl) extracts of roots and their components in HL-60 human leukemia cells. Compounds were isolated using solvent extraction and reverse-phase column chromatography, and their structures were confirmed by nuclear magnetic resonance (NMR) spectroscopy. The cytotoxicity effect of the compounds was tested on various cancer cell lines (HL-60, A549, and MCF-7). Two coumarins, (-)-isosamidin () and 3'S,4'S-disenecioylkhellactone (), were isolated through bioactivity-guided fractionation. Compound significantly induced apoptosis in HL-60 cells, as evidenced by an increase in the sub-G1 cell population and the initiation of both early and late apoptosis. Additional apoptotic markers, including reduced mitochondrial membrane potential (MMP) and increased cleavage of caspase-3, -8, and -9, were observed. These findings suggest that compound shows potential as a candidate for leukemia treatment, providing a promising natural-product-based approach to cancer therapy.

摘要

诱导肿瘤细胞发生程序性细胞死亡是癌症治疗的一种基本方法，促使人们广泛努力去发现具有抗癌特性的生物活性化合物。 是一种在东亚传统医学中使用的植物，据报道具有多种生物活性，包括抗癌作用。本研究旨在评估 根的甲醇/二氯甲烷（MeOH/CHCl）提取物及其成分对HL-60人白血病细胞的凋亡诱导作用。通过溶剂萃取和反相柱色谱法分离化合物，并通过核磁共振（NMR）光谱确认其结构。测试了这些化合物对各种癌细胞系（HL-60、A549和MCF-7）的细胞毒性作用。通过生物活性导向分级分离法分离出两种香豆素，（-）-异萨米丁（ ）和3'S，4'S-二异戊烯基凯拉内酯（ ）。化合物 显著诱导HL-60细胞凋亡，表现为亚G1期细胞群体增加以及早期和晚期凋亡的启动。还观察到其他凋亡标志物，包括线粒体膜电位（MMP）降低以及caspase-3、-8和-9的切割增加。这些发现表明化合物 显示出作为白血病治疗候选物的潜力，为基于天然产物的癌症治疗提供了一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/56cb4590b0dc/cells-13-01982-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/396856949f15/cells-13-01982-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/73dea48ec216/cells-13-01982-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/dde831d28130/cells-13-01982-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/6f6fb77fab1e/cells-13-01982-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/4d20a6a3b5c9/cells-13-01982-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/a123d2fe2a7a/cells-13-01982-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/45447e8ec741/cells-13-01982-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/56cb4590b0dc/cells-13-01982-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/396856949f15/cells-13-01982-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/73dea48ec216/cells-13-01982-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/dde831d28130/cells-13-01982-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/6f6fb77fab1e/cells-13-01982-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/4d20a6a3b5c9/cells-13-01982-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/a123d2fe2a7a/cells-13-01982-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/45447e8ec741/cells-13-01982-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfda/11639758/56cb4590b0dc/cells-13-01982-g008.jpg

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本文引用的文献

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Heliyon. 2023 Oct 14;9(10):e21032. doi: 10.1016/j.heliyon.2023.e21032. eCollection 2023 Oct.
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A Review on Anti-Tumor Mechanisms of Coumarins.香豆素类化合物抗肿瘤机制综述
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Isosamidin from Roots Prevents Methylglyoxal-Induced Glucotoxicity in Human Umbilical Vein Endothelial Cells via Suppression of ROS-Mediated Bax/Bcl-2.来自根部的异萨米丁通过抑制活性氧介导的Bax/Bcl-2，预防甲基乙二醛诱导的人脐静脉内皮细胞糖毒性。
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