Anti-Tumor Effect of Pinus massoniana Bark Proanthocyanidins on Ovarian Cancer through Induction of Cell Apoptosis and Inhibition of Cell Migration

PLoS One. 2015 Nov 5;10(11):e0142157. doi: 10.1371/journal.pone.0142157. eCollection 2015.

Abstract

Pinus massoniana bark proanthocyanidins (PMBPs), an active component isolated from Pinus massoniana bark, has been reported to possess a wide range of biochemical properties. Here, we investigated the anti-tumor effect of PMBPs on ovarian cancer. The results indicated that PMBPs significantly reduced the growth of ovarian cancer cells and induced dose-dependent apoptosis. The underlying mechanisms involved were elucidated to include the loss of mitochondrial membrane potential, down-regulation of the anti-apoptotic protein Bcl-2 and the activation of Caspase 3/9, suggesting that PMBPs triggered apoptosis through activation of mitochondria-associated apoptotic pathway. In addition, wound healing and transwell chamber assays revealed that PMBPs could suppress migration and invasion of ovarian cancer cells. PMBPs dramatically inhibited MMP-9 activity and expression, blocked the activity of NFκB and the activation of ERK1/2 and p38 MAPK. Our findings suggest that PMBPs has the potential to be developed as an anti-tumor drug for ovarian cancer treatment and/ or disease management.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Down-Regulation / drug effects
  • Female
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-kappa B / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Pinus / chemistry*
  • Plant Bark / chemistry*
  • Proanthocyanidins / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Antineoplastic Agents
  • NF-kappa B
  • Proanthocyanidins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • Caspase 9

Grant support

This work was funded by National Natural Science Foundation of China (No.81302282) (URL: http://www.nsfc.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.