Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression

Biosci Biotechnol Biochem. 2014;78(8):1402-11. doi: 10.1080/09168451.2014.921550. Epub 2014 Jun 18.

Abstract

Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression.

Keywords: Rubus coreanus Miquel; matrix metalloproteinase (MMP); metastasis; prostate cancer; tissue inhibitors of metalloproteinase(TIMP).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology*
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rubus / chemistry*
  • Tissue Inhibitor of Metalloproteinases / genetics
  • Tissue Inhibitor of Metalloproteinases / metabolism

Substances

  • Antineoplastic Agents
  • Plant Extracts
  • Tissue Inhibitor of Metalloproteinases
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinases