Resveratrol induces apoptosis of pancreatic cancers cells by inhibiting miR-21 regulation of BCL-2 expression

Clin Transl Oncol. 2013 Sep;15(9):741-6. doi: 10.1007/s12094-012-0999-4. Epub 2013 Jan 29.

Abstract

Objective: Resveratrol is an edible polyphenolic phytoalexin present in different plant species and plays important role in inhibiting proliferation and inducing apoptosis of pancreatic cancer cells. In this paper, the mechanism of resveratrol on PANC-1, CFPAC-1 and MIA Paca-2 cells apoptosis was examined.

Methods: We first evaluated the effect of resveratrol on viability of PANC-1, CFPAC-1 and MIA Paca-2 cells using MTT assay. Next, we performed real-time PCR to assess the effect of resveratrol on miR-21 expression. We also used Western blot to measure BCL-2 protein levels after down-regulation of miR-21 expression. Finally, we evaluated the effect of miR-21 on resveratrol-induced anti-tumor activity using miR-21 mimic.

Results: Resveratrol induced a significant inhibition of PANC-1, CFPAC-1 and MIA Paca-2 cells viability in a dose-dependent manner. Resveratrol also decreased the expression of miR-21. Besides, down-regulation of miR-21 expression can inhibit BCL-2 expression in PANC-1, CFPAC-1 and MIA Paca-2 cells. Over-expression of miR-21 expression can reverse down-regulation of BCL-2 expression and apoptosis induced by resveratrol.

Conclusions: In this study, we demonstrated that the effect of resveratrol on apoptosis is due to inhibiting miR-21 regulation of BCL-2 expression.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis*
  • Cell Line, Tumor
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / metabolism*
  • Pancreatic Ducts / drug effects
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Resveratrol
  • Stilbenes / pharmacology*
  • Tetrazolium Salts / chemistry
  • Thiazoles / chemistry

Substances

  • Antineoplastic Agents, Phytogenic
  • MIRN21 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • Stilbenes
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue
  • Resveratrol