Wogonin suppresses melanoma cell B16-F10 invasion and migration by inhibiting Ras-medicated pathways

PLoS One. 2014 Sep 9;9(9):e106458. doi: 10.1371/journal.pone.0106458. eCollection 2014.

Abstract

The patients diagnosed with melanoma have a bad prognosis for early regional invasion and distant metastases. Wogonin (5,7-dihydroxy-8-methoxyflavone) is one of the active components of flavonoids that extracts from Scutellariae radix. Several previous studies reported that wogonin possesses antitumor effect against leukemia, gastrointestinal cancer and breast cancer. In this study, we used melanoma cell B16-F10 to further investigate the anti-invasive and anti-migratory activity of wogonin. Our date showed that wogonin caused suppression of cell migration, adhesion, invasion and actin remodeling by inhibiting the expression of matrix metalloproteinase-2 and Rac1 in vitro. Wogonin also reduced the number of the tumor nodules on the whole surface of the lung in vivo. Furthermore, the examination of mechanism revealed that wogonin inhibited Extracellular Regulated protein Kinases and Protein Kinase B pathways, which are both medicated by Ras. Insulin-like growth factor-1-induced or tumor necrosis factor-α-induced invasion was also inhibited by wogonin. Therefore, the inhibitory mechanism of melanoma cell invasion by wogonin might be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects*
  • Cytoskeleton / drug effects
  • Cytoskeleton / pathology
  • Flavanones / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Melanoma, Experimental / pathology*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Tumor Necrosis Factor-alpha / pharmacology
  • ras Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Flavanones
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • ras Proteins
  • wogonin

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 91029744), Program for Changjiang Scholars and Innovative Research Team in University (IRT1193), the Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (No. JKGZ201101, SKLNMZZ201210, SKLNMZZCX201303 and SKLNMZZJQ201302), Fundamental Research Funds for the Central Universities (No. JKP2011003), and The National Science & Technology Major Project (No. 2012ZX09304-001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.