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Am J Chin Med. 2018 Oct 4:1-18. doi: 10.1142/S0192415X18500842. [Epub ahead of print]

Modified Ginseng Extract Induces Apoptosis in HepG2 Cancer Cells by Blocking the CXCL8-Mediated Akt/Nuclear Factor-[Formula: see text]B Signaling Pathway.

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* Department of Sasang Constitutional Medicine, Wonkwang University, Iksan 54538, Republic of Korea.
† Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University, Seoul 04763, Korea.
‡ Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea.
§ Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.
¶ Neuroscience Research Institute, Korea University College of Medicine, Seoul 136-705, Republic of Korea.
∥ East-West Cancer Center, Daejeon University, Daejeon 302-120, Korea.
** Department of Sasang Constitutional Medicine, Woosuk University, Wanju, Jeonbuk 55338, Republic of Korea.


The cytokine C-X-C motif chemokine ligand 8 (CXCL8) is produced in the tumor microenvironment and has an important role in cancer pathogenesis. CXCL8 activates the nuclear factor (NF)-[Formula: see text]B signaling. However, the role of NF-[Formula: see text]B inactivation in apoptosis induced by negative regulation of CXCL8 remains unclear. Here, we assessed the effects of MRGX on the transcriptional activity of NF-[Formula: see text]B and the expression of tumor necrosis factor (TNF)-[Formula: see text]-stimulated target genes in liver cancer cells. Furthermore, we found that modified regular ginseng extract (MRGX)-mediated inhibition of NF-[Formula: see text]B signaling induced apoptosis. Importantly, MRGX exerted strong activity, inhibiting TNF-[Formula: see text]-induced expression of Akt and NF-[Formula: see text]B in a concentration-dependent manner. Furthermore, MRGX inhibited the TNF-[Formula: see text]-induced expression of genes encoding CXCL8, CXCL1, inducible nitric oxide synthase and intercellular adhesion molecule 1. MRGX also dowregulated Akt activation, and there was a significant decrease in Akt activation in HepG2 cells treated with CXCL8 siRNA. Conversely, CXCL8 overexpression increased Akt activation in MRGX-treated HepG2 cells. When Akt was silenced, MRGX treatment of HepG2 cells overexpressing CXCL8 decreased nuclear translocation of NF-[Formula: see text]B, whereas Akt overexpression increased nuclear translocation of NF-[Formula: see text]B in MRGX-treated HepG2 cells. Moreover, MRGX negatively regulated the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote Bax activation, resulting in caspase-3 activation and apoptosis. Taken together, these results indicated that MRGX inhibited CXCL8-mediated Akt/NF-[Formula: see text]B signaling, which upregulated Bax activation and consequently induced apoptosis in HepG2 cells.


Akt; Apoptosis; C-X-C Motif Chemokine Ligand 8; Liver Cancer; MRGX; Modified Regular Ginseng Extract; Nuclear Factor-B


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