Ginsenoside-Rg2 exerts anti-cancer effects through ROS-mediated AMPK activation associated mitochondrial damage and oxidation in MCF-7 cells

• Published in: Archives of pharmacal research Vol. 44; no. 7; pp. 702 - 712
• Main Authors: Jeon, Hyesu, Jin, Yujin, Myung, Chang-Seon, Heo, Kyung-Sun
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.07.2021; 대한약학회
• Subjects: AMP-Activated Protein Kinases - metabolism; Apoptosis - drug effects; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Drug Screening Assays, Antitumor; G1 Phase Cell Cycle Checkpoints - drug effects; Ginsenosides - pharmacology; Ginsenosides - therapeutic use; Humans; MCF-7 Cells; Medicine; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - pathology; Oxidation-Reduction - drug effects; Pharmacology/Toxicology; Pharmacy; Reactive Oxygen Species - metabolism; Research Article; Signal Transduction - drug effects; 약학; AMPK; Reactive oxygen species; Breast cancer; Ginsenoside-Rg2; Cell cycle; Mitochondrial membrane potential
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-021-01345-3

In this study, we investigated the anti-cancer effects of ginsenoside Rg2 (G-Rg2) and its underlying signaling pathways in breast cancer (BC) cells. G-Rg2 significantly induced cytotoxicity and reactive oxygen species (ROS) production in MCF-7 cells among various types of BC cells including HCC1428, T47D, and BT-549. G-Rg2 significantly inhibited protein and mRNA expression of cell cycle G1-S phase regulators, including p-Rb, cyclin D1, CDK4, and CDK6, whereas it enhanced the protein and mRNA expression of cell cycle arrest and apoptotic molecules including cleaved PARP, p21, p27, p53 and Bak through ROS production. These effects were abrogated by the antioxidant N-acetyl-I-cysteine, or NADPH oxidase inhibitors, such as diphenyleneiodonium chloride and apocynin. Interestingly, G-Rg2 induced mitochondrial damage by reducing the membrane potential. G-Rg2 further activated the ROS-sensor protein, AMPK and downstream targets of AMPK activation, including PGC-1α, FOXO1, and IDH2, and downregulated mTOR activation and antioxidant response element-driven luciferase activity. Together, our data demonstrate that G-Rg2 mediates anti-cancer effects by activating cell cycle arrest and signaling pathways related to mitochondrial damage-induced ROS production and apoptosis.