Resveratrol inhibits pancreatic cancer cell proliferation through transcriptional induction of macrophage inhibitory cytokine-1

J Surg Res. 2007 Apr;138(2):163-9. doi: 10.1016/j.jss.2006.05.037. Epub 2007 Jan 25.


Introduction: Resveratrol is a phenolic compound found in grape skins, mulberries, and certain nuts that has been shown to have antitumorigenic and anti-inflammatory properties. Macrophage inhibitory cytokine (MIC-1) is a member of the transforming growth factor beta (TGF-beta) superfamily that has been shown to have antitumorigenic activity and is up-regulated in resveratrol-treated cancer cells. Resveratrol inhibits proliferation of human pancreatic cancer cells; however, the exact mechanism of action is not known. In this study, we investigated the role of MIC-1 in resveratrol-induced growth inhibition of human pancreatic cancer cell lines.

Methods and results: Proliferation assays conducted with resveratrol-treated human pancreatic cancer cell lines (CD18 and S2-013) at 24, 48, and 72 h revealed inhibition of cell proliferation compared to controls. Using oligonucleotide microarray analysis, we identified marked up-regulation of MIC-1 gene expression in resveratrol-treated human pancreatic cancer S2-013 cells. Real-time RT-PCR performed in CD18 and S2-013 cells treated with resveratrol (0-100 mum) for 24 h confirmed concentration and time-dependent up-regulation of expression of one particular gene, MIC-1. Both cell lines pretreated with actinomycin D (a transcriptional inhibitor) and then resveratrol had reduced up-regulation of MIC-1 gene expression compared to those treated with resveratrol alone. Finally, resveratrol-induced growth inhibition was abolished in CD18 cells transfected with MIC-1 short interfering RNA.

Conclusions: Resveratrol up-regulates MIC-1 gene expression in part at the transcriptional level in pancreatic cancer cells. Furthermore, MIC-1 appears to play a key role in resveratrol-induced growth inhibition in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Bone Morphogenetic Proteins / genetics*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Dactinomycin / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Growth Differentiation Factor 15
  • Humans
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Oligonucleotide Array Sequence Analysis
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / physiopathology
  • RNA, Small Interfering
  • Resveratrol
  • Stilbenes / pharmacology*
  • Transcription, Genetic / drug effects
  • Transfection
  • Up-Regulation / drug effects


  • Antineoplastic Agents, Phytogenic
  • Bone Morphogenetic Proteins
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Small Interfering
  • Stilbenes
  • Dactinomycin
  • Resveratrol