Modified Ginseng Extract Induces Apoptosis in HepG2 Cancer Cells by Blocking the CXCL8-Mediated Akt/Nuclear Factor-[Formula: see text]B Signaling Pathway.
Am J Chin Med
; : 1-18, 2018 Oct 04.
Article
em En
| MEDLINE
| ID: mdl-30284465
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Am J Chin Med
Ano de publicação:
2018
Tipo de documento:
Article