Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Rg3-enriched red ginseng extracts enhance apoptosis in CoCl2-stimulated breast cancer cells by suppressing autophagy

  • Yun-Jeong Jeong (Research Institute of Biomedical Engineering and Department of cell Biology, Catholic University of Daegu School of Medicine) ;
  • Mi-Hee Yu (Research Institute of Biomedical Engineering and Department of cell Biology, Catholic University of Daegu School of Medicine) ;
  • Yuna Cho (Research Institute of Biomedical Engineering and Department of cell Biology, Catholic University of Daegu School of Medicine) ;
  • Min-Young Jo (Research Institute of Biomedical Engineering and Department of cell Biology, Catholic University of Daegu School of Medicine) ;
  • Kwon-Ho Song (Research Institute of Biomedical Engineering and Department of cell Biology, Catholic University of Daegu School of Medicine) ;
  • Yung Hyun Choi (Department of Biochemistry, College of Korean Medicine, Dong-Eui University) ;
  • Taeg Kyu Kwon (Department of Immunology, School of Medicine, Keimyung University) ;
  • Jong-Young Kwak (Department of Pharmacology, School of Medicine, Ajou University) ;
  • Young-Chae Chang (Research Institute of Biomedical Engineering and Department of cell Biology, Catholic University of Daegu School of Medicine)
  • Received : 2022.12.14
  • Accepted : 2023.06.06
  • Published : 2024.01.01
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Abstract

Background: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl2, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl2-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl2-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic.

Keywords

Acknowledgement

This research was supported by the Korean Society of Ginseng (2021) and National Research Foundation of Korea (NRF) grants funded by the Korean government (MSIT) (2022R1A4A5032702)

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