Transcriptome Analyses of the Anti-Proliferative Effects of 20(S)-Ginsenoside Rh2 on HepG2 Cells

Zhang, Ji; Li, Weibo; Yuan, Qiaoyun; Zhou, Jing; Zhang, Jianmei; Cao, Yufeng; Fu, Guangbo; Hu, Weicheng

doi:10.3389/fphar.2019.01331

Cited by 16 publications

(11 citation statements)

References 44 publications

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“…Apoptosis may not the main way for the death of many cancers response to common treatments ( Brown and Attardi, 2005 ). G-Rh2 were reported to induces apoptosis of many cancer cells, such as human epidermoid carcinoma A431cells ( Park et al, 2010 ), human malignant melanoma A375-S2 cells ( Fei et al, 2002 ), and hepatocellular carcinoma HepG2 cells ( Zhang et al, 2019 ). In order to determine whether G-Rh2 can regulates A549 cell death by inducing apoptosis in this study, A549 cells treated with 10, 20, and 40 μM G-Rh2 were stained by Annexin-PI based on a flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

Network Pharmacology-Based Prediction and Verification of Ginsenoside Rh2-Induced Apoptosis of A549 Cells via the PI3K/Akt Pathway

et al. 2022

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Ginsenoside Rh2 (G-Rh2), a rare protopanaxadiol (PPD)-type triterpene saponin, from Panax ginseng has anti-proliferation, anti-invasion, and anti-metastatic activity. However, the mechanisms by which G-Rh2 induces apoptosis of lung cancer cells are unclear. In the present work, a G-Rh2 target-lung cancer network was constructed and analyzed by the network pharmacology approach. A total of 91 compound-targets of G-Rh2 was obtained based on the compound-target network analysis, and 217 targets were identified for G-Rh2 against lung cancer by PPI network analysis. The 217 targets were significantly enriched in 103 GO terms with FDR <0.05 as threshold in the GO enrichment analysis. In KEGG pathway enrichment analysis, all the candidate targets were significantly enriched in 143 pathways, among of which PI3K-Akt signaling pathway was identified as one of the top enriched pathway. Besides, G-Rh2 induced apoptosis in human lung epithelial (A549) cells was verified in this work. G-Rh2 significantly inhibited the proliferation of A549 cells in a dose-dependent manner, and the apoptosis rate significantly increased from 4.4% to 78.7% using flow cytometry. Western blot analysis revealed that the phosphorylation levels of p85, PDK1, Akt and IκBα were significantly suppressed by G-Rh2. All the experimental findings were consistent with the network pharmacology results. Research findings in this work will provide potential therapeutic value for further mechanism investigations.

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Section: Resultsmentioning

confidence: 99%

Network Pharmacology-Based Prediction and Verification of Ginsenoside Rh2-Induced Apoptosis of A549 Cells via the PI3K/Akt Pathway

et al. 2022

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“…It can increase autophagy of HepG2 and Huh7 cells, inhibit β-catenin signaling, regulate immune response and down regulate VEGF, which eventually inhibit cellular growth and migration. 27,28 Icaritin, a natural isopentene flavonoid also known as 3,5,7-trihydroxy-2-(4-hydroxymethylphenyl)-8-(3-methylbutenyl-2)-1,2-benzopyranone-4, is the bioactive compound of Epimedium. It inhibits tumor cell proliferation and induces apoptosis by targeting the IL-6/ STAT3, IGF1/STAT3 and MAPK/ERK signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Clinical Trials of New Drugs for Liver Diseases in China

Lin¹,

Li²

2021

DDDT

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Background: Liver diseases are a major public health concern worldwide, and the development of novel therapeutic drugs is an important research focus. But no overview has been conducted so far on the current research and development for liver-specific drugs in China, and the actual situation regarding the development and evaluation of new drugs in clinical trials. Methods: The information of all clinical trials on liver diseases were obtained through the "Pharmaceutical Clinical Trial Registration and Information Disclosure Platform" before December 31, 2020. Results: A total of 751 clinical trials on liver disease-related drugs were published on the above platform, including 574 chemical drugs, 128 biological products, and 49 traditional Chinese medicine (TCM)/natural drugs. The number of annual registrations has increased on an annual basis. The main indications for these clinical trials are viral hepatitis, liver malignancies, liver abscess, liver transplantation, congenital liver metabolic disease, and other hepatitis-related diseases. Hepatitis B, hepatitis C and liver cancer accounted for 72.4% of the total clinical trials, and the majority are related to generic drug research. There are 103 innovative drugs currently in clinical testing, mainly for hepatitis B, hepatitis C and hepatocellular carcinoma. Conclusion:The stronger macro-control is required for the clinical trials conducted in China, and it is necessary to identify new therapeutic targets and develop novel drugs for the key liver diseases, as well as preventive hepatitis C vaccines, and targeted therapy, TCM/ natural drugs and immunotherapy for liver cancer.

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“…Ginsenoside Rh2 also inhibited proliferation and promotes apoptosis of H1299 cells by inducing endoplasmic reticulum stress mediated by ROS (53). The synergistic effect of autophagy and β-catenin signal transduction inhibited the proliferation and migration of human liver cancer HepG2, Hep3B and Huh7 cells, and restrained tumor growth in HepG2-xenografted mice (54,55). Ginsenoside Rh2 inhibited cell proliferation, promoted apoptosis and reversed the resistance of colon cancer to the chemotherapeutic drug oxaliplatin (56).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rh2 inhibits HeLa cell energy metabolism and induces apoptosis by upregulating voltage‑dependent anion channel 1

et al. 2020

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20(S)-Ginsenoside Rh2 [20(S)-GRh2], one of the main active components of Panax ginseng, induces apoptosis in a wide range of cancer cell types. The present study found that 20(S)-GRh2 reduces mitochondrial membrane potential, decreases adenosine triphosphate generation and induces reactive oxygen species in HeLa cervical cancer cells. In addition, 20(S)-GRh2 activated mitochondrion-dependent apoptosis and inhibited both mitochondrial oxidative phosphorylation and glycolysis in HeLa cells. It was found that voltage-dependent anion channel 1 (VDAC1) expression was significantly upregulated by 20(S)-GRh2 treatment, while hexokinase 2 expression was downregulated and segregated from the mitochondria. Furthermore, 20(S)-GRh2 promoted Bax transport from the cytoplasm to the mitochondria, and knockdown of VdAc1 inhibited Bax transport and apoptosis. These results suggest that VdAc1 is a novel target of 20(S)-GRh2. The present study provides a better understanding of the mechanistic link between cervical cancer metabolism and growth control, and these results may facilitate the development of new treatments for cervical cancer.

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Transcriptome Analyses of the Anti-Proliferative Effects of 20(S)-Ginsenoside Rh2 on HepG2 Cells

Cited by 16 publications

References 44 publications

Network Pharmacology-Based Prediction and Verification of Ginsenoside Rh2-Induced Apoptosis of A549 Cells via the PI3K/Akt Pathway

Network Pharmacology-Based Prediction and Verification of Ginsenoside Rh2-Induced Apoptosis of A549 Cells via the PI3K/Akt Pathway

Analysis of Clinical Trials of New Drugs for Liver Diseases in China

Ginsenoside Rh2 inhibits HeLa cell energy metabolism and induces apoptosis by upregulating voltage‑dependent anion channel 1

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