Resveratrol suppresses tumor progression via the regulation of indoleamine 2,3-dioxygenase

Biochem Biophys Res Commun. 2013 Feb 8;431(2):348-53. doi: 10.1016/j.bbrc.2012.12.093. Epub 2013 Jan 3.

Abstract

This study showed the potential of resveratrol to inhibit the expression and activity of interferon-γ (IFN-γ)-induced indoleamine 2,3-dioxygenase (IDO) in bone marrow-derived dendritic cells (BMDCs). The mechanism of suppression was associated with the activity of Janus kinase/signal transducers and activators of transcription (JAK/STAT) and protein kinase Cδ (PKCδ). In addition, resveratrol-mediated IDO suppression in IFN-γ-stimulated BMDCs appears to play a pivotal role in anti-tumor activity through the regulation of CD8(+) T cell polarization and cytotoxic T lymphocyte (CTL) activity. Systemic administration of resveratrol suppressed tumor growth in EG7 thymoma-bearing mice in an IDO-dependent manner. Taken together, resveratrol not only regulates immune response through the regulation of IDO in a JAK/STAT1- and PKCδ-dependent manner, but also modulates the IDO-mediated immune tolerance in EG7 thymoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Dendritic Cells / immunology*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors*
  • Janus Kinases / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Resveratrol
  • STAT1 Transcription Factor / metabolism
  • Stilbenes / administration & dosage*
  • Tumor Escape / drug effects*

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • STAT1 Transcription Factor
  • Stilbenes
  • Janus Kinases
  • Proto-Oncogene Proteins c-akt
  • Resveratrol