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人参皂苷AD-1和AD-2的立体特异性通过诱导线粒体功能障碍和活性氧介导的细胞凋亡显示出抗癌活性。

Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis.

作者信息

Wang Xude, Ding Meng, Zhao Hong, Zhou Mengru, Lu Xuan, Sun Yuanyuan, Zhang Qinggao, Zhao Yuqing, Wang Ruoyu

机构信息

Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China.

Chronic Disease Research Center, Medical College, Dalian University, Dalian 116622, China.

出版信息

Molecules. 2023 Sep 19;28(18):6698. doi: 10.3390/molecules28186698.

DOI:10.3390/molecules28186698
PMID:37764474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10536438/
Abstract

In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20()-AD-1, 20()-AD-2, 20()-AD-1 and 20()-AD-2) were investigated. The results indicated that all of the four compounds obviously suppressed the viability of various cancer cells, and the anti-cancer activity of 20()-AD-1 and 20()-AD-2 was significantly better than 20()-AD-1 and 20()-AD-2, especially for gastric cancer cells (BGC-803). Then, the differences in the anti-cancer mechanisms of the isomers were investigated. The data showed that 20()-AD-1 and 20()-AD-2 induced apoptosis and decreased MMP, up-regulated the expression of cytochrome C in cytosol, transferred Bax to the mitochondria, suppressed oxidative phosphorylation and glycolysis and stimulated reactive oxygen species (ROS) production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. However, 20()-AD-1 and 20()-AD-2 barely exhibited the same results. The results indicated that 20()-AD-1 and 20()-AD-2 suppressed cellular energy metabolism and caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in. Above all, the data support the development of 20()-AD-1 and 20()-AD-2 as potential agents for human gastric carcinoma therapy.

摘要

本文研究了AD - 1和AD - 2的异构体（20()-AD - 1、20()-AD - 2、20()-AD - 1和20()-AD - 2）的抗癌活性及分子机制。结果表明，这四种化合物均能明显抑制多种癌细胞的活力，且20()-AD - 1和20()-AD - 2的抗癌活性明显优于20()-AD - 1和20()-AD - 2，尤其对胃癌细胞（BGC - 803）。随后，研究了异构体抗癌机制的差异。数据显示，20()-AD - 1和20()-AD - 2诱导细胞凋亡并降低线粒体膜电位（MMP），上调胞质中细胞色素C的表达，将Bax转移至线粒体，抑制氧化磷酸化和糖酵解并刺激活性氧（ROS）生成。活性氧清除剂N - 乙酰半胱氨酸可减弱细胞凋亡。然而，20()-AD - 1和20()-AD - 2几乎未表现出相同结果。结果表明，20()-AD - 1和20()-AD - 2通过线粒体途径抑制细胞能量代谢并导致细胞凋亡，这可能与ROS生成有关。综上所述，这些数据支持将20()-AD - 1和20()-AD - 2开发为治疗人类胃癌的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/a02cea5a50a8/molecules-28-06698-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/f08080e4ad03/molecules-28-06698-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/8177dd3950bc/molecules-28-06698-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/18f0436d201e/molecules-28-06698-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/0e458ab45c24/molecules-28-06698-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/a02cea5a50a8/molecules-28-06698-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/f08080e4ad03/molecules-28-06698-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/8177dd3950bc/molecules-28-06698-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/18f0436d201e/molecules-28-06698-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/0e458ab45c24/molecules-28-06698-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10536438/a02cea5a50a8/molecules-28-06698-g005.jpg

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