Systemic and molecular analysis dissect the red ginseng induction of apoptosis and autophagy in HCC as mediated with AMPK

Young Woo Kim; Seon Been Bak; Won-Yung Lee; Su Jin Bae; Eun Hye Lee; Ju-Hye Yang; Kwang Youn Kim; Chang Hyun Song; Sang Chan Kim; Un-Jung Yun; Kwang Il Park

doi:10.1016/j.jgr.2023.02.002

Systemic and molecular analysis dissect the red ginseng induction of apoptosis and autophagy in HCC as mediated with AMPK

J Ginseng Res. 2023 May;47(3):479-491. doi: 10.1016/j.jgr.2023.02.002. Epub 2023 Feb 23.

Authors

Young Woo Kim^{1

2}, Seon Been Bak¹, Won-Yung Lee¹, Su Jin Bae¹, Eun Hye Lee³, Ju-Hye Yang⁴, Kwang Youn Kim⁴, Chang Hyun Song⁵, Sang Chan Kim⁵, Un-Jung Yun¹, Kwang Il Park⁶

Affiliations

¹ School of Korean Medicine, Dongguk University, Gyeongju, Republic of Korea.
² Department of Computer Science and Engineering, Kyungpook National University, Daegu, Korea.
³ College of Medicine, Kyungpook National University, Daegu, Republic of Korea.
⁴ Korean Medicine (KM) Application Center, Korea Institute of Oriental Medicine, Daegu, Republic of Korea.
⁵ MRC center, College of Korean Medicine, Daegu Haany University, Gyeongsan, Republic of Korea.
⁶ Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea.

Abstract

Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology.

Materials and methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins.

Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy.

Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.

Keywords: AMPK; Apoptosis; HCC; Network pharmacology; Red ginseng.