The chemoadjuvant potential of grape seed procyanidins on p53-related cell death in oral cancer cells

J Oral Pathol Med. 2012 Apr;41(4):322-31. doi: 10.1111/j.1600-0714.2011.01103.x. Epub 2011 Nov 21.

Abstract

Background: To clarify the efficacy of grape seed procyanidin (GSP) on antiproliferative effects related to p53 functional status of oral squamous cell carcinoma (OSCC) for its chemoadjuvant potential.

Methods: We used GSP to investigate SCC-25 cells with wild-type p53 gene and OEC-M1 cells with mutant p53 gene for the assessment of antiproliferative effects including cell viability, cell cycle, apoptosis, migration and invasion potential, and alterations of associated oncoproteins involved in cellular and molecular events.

Results: The findings suggest that GSP on OEC-M1 cells leads to cell cycle arrest by increasing the expression of p21(Cip1) /p27(Kip1) protein without functioning mitochondria-mediated apoptosis, whereas GSP on SCC-25 cells inhibits cell proliferation via both G1-phase arrest and mitochondria-mediated apoptosis in a dose-dependent manner as a result of alterations of Bcl-2. GSP also inhibits the migration and invasion of both cells, which are associated with the suppression of matrix metalloproteinases (MMPs), MMP-2 and MMP-9.

Conclusion: Antiproliferative effectiveness of GSP is closely associated with the p53 status of OSCC cells. GSP displays chemoadjuvant potential via cell cycle blockage and apoptotic induction. Our findings clearly suggest that GSP may play a role as a novel chemopreventive or therapeutic agent for OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / pathology*
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin-Dependent Kinase Inhibitor p21 / drug effects
  • Cyclin-Dependent Kinase Inhibitor p27 / drug effects
  • Dose-Response Relationship, Drug
  • G1 Phase / drug effects
  • Grape Seed Extract / pharmacology*
  • Humans
  • Matrix Metalloproteinase 2 / drug effects
  • Matrix Metalloproteinase 9 / drug effects
  • Mitochondria / drug effects
  • Mouth Neoplasms / pathology*
  • Neoplasm Invasiveness
  • Oncogene Proteins / drug effects
  • Plant Preparations / pharmacology*
  • Point Mutation / genetics
  • Proanthocyanidins / pharmacology*
  • Protein Kinase Inhibitors / analysis
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Tumor Suppressor Protein p53 / drug effects*
  • Tumor Suppressor Protein p53 / genetics
  • Vitis*

Substances

  • Anticarcinogenic Agents
  • Antineoplastic Agents
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • Oncogene Proteins
  • Plant Preparations
  • Proanthocyanidins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p27
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9