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

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

doi:10.3390/molecules28186698

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

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

Authors

Xude Wang^{1

2}, Meng Ding³, Hong Zhao⁴, Mengru Zhou², Xuan Lu⁴, Yuanyuan Sun⁵, Qinggao Zhang⁶, Yuqing Zhao^{5

6}, Ruoyu Wang¹

Affiliations

¹ Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China.
² Chronic Disease Research Center, Medical College, Dalian University, Dalian 116622, China.
³ College of Chemistry and Chemical Engineering, Cangzhou Normal University, Cangzhou 061000, China.
⁴ China College of Life and Health, Dalian University, Dalian 116622, China.
⁵ School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, China.
⁶ Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, China.

Abstract

In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(R)-AD-1, 20(R)-AD-2, 20(S)-AD-1 and 20(S)-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(R)-AD-1 and 20(R)-AD-2 was significantly better than 20(S)-AD-1 and 20(S)-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(R)-AD-1 and 20(R)-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(S)-AD-1 and 20(S)-AD-2 barely exhibited the same results. The results indicated that 20(R)-AD-1 and 20(R)-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(R)-AD-1 and 20(R)-AD-2 as potential agents for human gastric carcinoma therapy.

Keywords: AD-1 and AD-2; ROS; anti-cancer; apoptosis; isomers.

Grants and funding

This research was partly supported by Hebei Natural Science Foundation (Youth Science Foundation Project) supported by the Natural Science Foundation of Hebei Province, title of the Project: Discovery and Structure-activity Relationship Study of Lead Compounds Targeting Ovarian Cancer PARP Inhibitor, project Number H2022110011; and Dalian Science and Technology Innovation Fund Project supported by Dalian Municipal Government, title of the Project: Screening and Mechanism Research of Effective Components of Natural Drugs for Anti-Osteoporosis Project, number 2022JJ12WZ059.