title: Wogonin inhibits the proliferation and invasion, and induces the apoptosis of HepG2 and Bel7402 HCC cells through NF‑κB/Bcl-2, EGFR and EGFR downstream ERK/AKT signaling.
abstract: The anticancer effects of the natural flavonoid, wogonin, have been reported. However, its molecular mechanisms of action have not yet been fully explored. In the present study, we aimed to examine the molecular mechanisms of action of wogonin and its effects on the biological behavior of the HepG2 and Bel7402 hepatocellular carcinoma (HCC) cell lines. We also examined the effects of wogonin on nuclear factor-κB (NF-κB)/Bcl-2 and epidermal growth factor receptor (EGFR) signaling, as well as on downstream pathways of EGFR, namely extracellular signal-regulated kinase (ERK)/AKT signaling. We found that treatment with wogonin inhibited the proliferation and invasion, and induced the apoptosis of the HepG2 and Bel7402 cells. In addition, treatment with wogonin decreased cyclin D1, cyclin E, CDK4/6, Bcl-2 and matrix metalloproteinase 2 (MMP2) expression, and promoted the cleavage of caspase-3 and caspase-9 in a concentration-dependent manner. Further experiments revealed that wogonin inhibited NF-κB/Bcl-2 signaling by decreasing the IκB and p65 phosphorylation levels. Wogonin also inhibited the activation of the EGFR (Tyr845) signaling pathway, and that of downstream pathways of EGFR, namely ERK/AKT/MMP2 signaling. The depletion of EGFR by siRNA partly abolished the inhibitory effects of wogonin on cyclin D1, MMP2 expression. On the whole, our our findings demonstrate that wogonin effectively suppresses the proliferation, invasion and survival of HCC cells through the modulation of the NF-κB and EGFR signaling pathways.
authors: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors: Xiaodong
authors: X
authors: Liu
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors: Shuo
authors: S
authors: Tian
authors: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors: Mei
authors: M
authors: Liu
authors: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors: Lingyan
authors: L
authors: Jian
authors: Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning, P.R. China.
authors: Limei
authors: L
authors: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018797:Cell Cycle Proteins; D044950:Flavanones; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C085514:wogonin