Rubus idaeus extract suppresses migration and invasion of human oral cancer by inhibiting MMP-2 through modulation of the Erk1/2 signaling pathway

Environ Toxicol. 2017 Mar;32(3):1037-1046. doi: 10.1002/tox.22302. Epub 2016 Jun 20.


Raspberries (Rubus idaeus L.) have been extensively studies worldwide because of their beneficial effects on health. Recently reports indicate that crude extracts of Rubus idaeus (RIE) have antioxidant and anticancer ability. The aim of this study was to evaluate the mechanism of its antimetastatic ability in oral cancer cells. In this study, SCC-9 and SAS oral cancer cells were subjected to a treatment with RIE and then analyzed the effect of RIE on migration and invasion. The addition of RIE inhibited the migration and invasion ability of oral cancer cells. Real time PCR, western blot and zymography analysis demonstrated that mRNA, protein expression and enzyme activity of matrix metalloproteinases-2 (MMP-2) were down-regulated by RIE. Moreover, the phosphorylation of Focal adhesion kinase (FAK), src, and extracellular signal-regulated kinase (ERK) were inhibited after RIE treatment. In conclusion, these results demonstrated that RIE exerted an inhibitory effect of migration and invasion in oral cancer cells and alter metastasis by suppression of MMP-2 expression through FAK/Scr/ERK signaling pathway. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1037-1046, 2017.

Keywords: MMP-2; Rubus idaeus; migration; oral cancer.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Adhesion / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 2 / physiology*
  • Matrix Metalloproteinase 9 / metabolism
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Plant Extracts / pharmacology*
  • Rubus / chemistry*
  • Signal Transduction / drug effects


  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9