Crude extract of Euphorbia formosana inhibits the migration and invasion of DU145 human prostate cancer cells: The role of matrix metalloproteinase-2/9 inhibition via the MAPK signaling pathway

Mol Med Rep. 2013 May;7(5):1403-8. doi: 10.3892/mmr.2013.1380. Epub 2013 Mar 20.

Abstract

Prostate cancer is a common worldwide health problem in males with a poor prognosis due in part to tumor invasion and migration. The crude extract of Euphorbia formosana (CEEF) has been used for the treatment of numerous diseases, however, its effects on the migration and invasion of prostate cancer cells have yet to be examined. In the present study, we investigated the effects of CEEF on the migration and invasion of DU145 human prostate cancer cells in vitro. The wound healing assay and the Matrigel-uncoated migration assay were used to examine the migration of cancer cells. Western blotting was used to examine the levels of proteins associated with migration and invasion, and gelatin zymography was used to examine the secretion levels of matrix metalloproteinases-2 and -9 (MMP‑2/9) from DU145 cells following exposure to CEEF. The results indicated that CEEF suppressed the migration and invasion of DU145 prostate cancer cells and that these effects are exerted in a concentration- and time-dependent manner. CEEF inhibited the ERK1/2, p38, JNK, SOS1, PKC, PI3K and MMP-2/9 protein expression in DU145 cells. The results demonstrated that CEEF suppressed the migration and invasion of DU145 cells through inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway resulting in the inhibition of MMP-2/9 in DU145 human prostate cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Cell Survival / drug effects
  • Complex Mixtures / pharmacology
  • Complex Mixtures / therapeutic use*
  • Euphorbia / chemistry*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MAP Kinase Signaling System* / drug effects
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Complex Mixtures
  • Matrix Metalloproteinase Inhibitors
  • Neoplasm Proteins
  • Plant Extracts
  • RNA, Messenger
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9