Melittin suppresses EGF-induced cell motility and invasion by inhibiting PI3K/Akt/mTOR signaling pathway in breast cancer cells

Food Chem Toxicol. 2014 Jun:68:218-25. doi: 10.1016/j.fct.2014.03.022. Epub 2014 Mar 25.

Abstract

Bee venom is a natural compound produced by the honey bee (Apis mellifera), and has been reported as having the biological and pharmacological activities, including anti-bacterial, anti-viral and anti-inflammation. In the present study, the inhibitory effects of bee venom and its major peptide components on the tumor invasion were demonstrated. It was confirmed the inhibitory effects of bee venom, melittin, and apamin on the EGF-induced invasion of breast cancer cells. Transwell invasion and wound-healing assays showed that bee venom and melittin significantly inhibits the EGF-induced invasion and migration of breast cancer cells. Also, bee venom and melittin reduced the EGF-stimulated F-actin reorganization at the leading edge, but apamin did not affect. Particularly, melittin inhibited the EGF-induced MMP-9 expression via blocking the NF-κB and PI3K/Akt/mTOR pathway. In addition, melittin significantly suppressed the EGF-induced FAK phosphorylation through inhibition of mTOR/p70S6K/4E-BP1 pathway. These results suggest that inhibitory effects of melittin on breast cancer cell motility and migration may be related to the inhibition of mTOR pathway.

Keywords: Bee venom; Cancer invasion; FAK; MMP; Melittin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Epidermal Growth Factor / pharmacology*
  • Female
  • Focal Adhesion Kinase 1 / genetics
  • Focal Adhesion Kinase 1 / metabolism
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Melitten / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Melitten
  • Epidermal Growth Factor
  • MTOR protein, human
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • MMP9 protein, human
  • Matrix Metalloproteinase 9