Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2

Wang, Yushi; Zhu, Hongyan; Li, He; Li, Yang; Zhao, Bing

doi:10.1016/j.jgr.2018.04.002

Cited by 22 publications

(20 citation statements)

References 34 publications

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“…For example, (20S)G-Rh2 has been identified to inhibit Annexin A2 binding to NF-κB p50 subunit [ 35 ]. Subsequently, ginsenoside compound K (CK), G-Rk1, and G-Rg5 were also confirmed to inhibit NF-κB by targeting Annexin A2 [ 36 , 37 ]. There is a phenomenon that the addition of bovine serum albumin (BSA) reduces the cytotoxic effects of compounds on various kinds of cells appearing in the experiments of cell viability.…”

Section: Discussionmentioning

confidence: 99%

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Chen

Yang

2021

Molecules

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Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.

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Section: Discussionmentioning

confidence: 99%

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Chen

Yang

2021

Molecules

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“…Also, CK induced apoptosis and ERS in liver cancer cells and xenografted mice by modulating signal transducers and activators of transcription-3 (STAT3) activation [ 85 ]. Another study showed for the first time that CK targeted annexin A2, which leads to inhibition of NF-κB [ 86 ]. Compound K enhanced ERS and calcium release by ryanodine receptors leading to apoptosis in lung cancer cells of humans.…”

Section: Health-promoting Activitiesmentioning

confidence: 99%

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Sharma

Lee

2020

Biomolecules

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Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The review summarizes health-promoting in vitro and in vivo studies of CK between 2015 and 2020, including hepatoprotective, anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer, neuroprotective, anti-aging/skin protective, and others. Clinical trial data are minimal and are primarily based on CK-rich fermented ginseng. Besides, numerous preclinical and clinical studies indicating the pharmacokinetic behavior of CK, its parent compound (Rb1), and processed ginseng extracts are also summarized. With the limited evidence available from animal and clinical studies, it can be stated that CK is safe and well-tolerated. However, lower water solubility, membrane permeability, and efflux significantly diminish the efficacy of CK and restrict its clinical application. We found that the use of nanocarriers and cyclodextrin for CK delivery could overcome these limitations as well as improve the health benefits associated with them. However, these derivatives have not been clinically evaluated, thus requiring a safety assessment for human therapy application. Future studies should be aimed at investigating clinical evidence of CK.

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“…In previous studies, ginsenoside CK has been demonstrated to have pleiotropic activity in various cancers [27]. Extensive mechanistic studies have shown that ginsenoside CK can induce apoptosis and cell cycle arrest, inhibit angiogenesis and sensitize human colon cancer, lung cancer, breast cancer, glioblastoma, liver cancer and more [28][29][30][31][32]. However, the inhibitory activities of ginsenoside CK on cancer metastasis have been less reported.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside CK Inhibits Hypoxia-Induced Epithelial–Mesenchymal Transformation through the HIF-1α/NF-κB Feedback Pathway in Hepatocellular Carcinoma

Zhang

Fan

2021

Foods

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Hepatocellular carcinoma (HCC) is a kind of malignant tumor with high morbidity and mortality rates worldwide. Epithelial–mesenchymal transformation (EMT) is crucial for HCC progression and prognosis. Characteristics of the tumor microenvironment, such as hypoxia, and excessive activation of the NF-κB signaling pathway have been identified as the key inducers of EMT in HCC. In our study, we verified the crosstalk between HIF-1α signaling and NF-κB pathway and their effects on EMT in HCC cells. The results show that CoCl2-induced hypoxia could promote IκB phosphorylation to activate NF-κB signaling and vice versa. Moreover, we found that ginsenoside CK, a metabolite of protopanaxadiol saponins, could inhibit the proliferation and colony formation of different HCC cell lines. Furthermore, ginsenoside CK could impair the metastatic potential of HCC cell lines under hypoxic conditions. Mechanistically, ginsenoside CK suppressed HIF-1α/NF-κB signaling and expression level of EMT-related proteins and cytokines in hypoxia-induced or TNFα-stimulated HCC cell lines. An in vivo study revealed that the oral delivery of ginsenoside CK could inhibit the growth of xenograft tumors and block HIF-1α and NF-κB signaling as well as EMT marker expression. Our study suggests that ginsenoside CK is a potential therapy for HCC patients that functions by targeting the HIF-1α/NF-κB crosstalk.

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Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2

Cited by 22 publications

References 34 publications

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Ginsenoside CK Inhibits Hypoxia-Induced Epithelial–Mesenchymal Transformation through the HIF-1α/NF-κB Feedback Pathway in Hepatocellular Carcinoma

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