Curcumin blocks interleukin-1 signaling in chondrosarcoma cells

PLoS One. 2014 Jun 5;9(6):e99296. doi: 10.1371/journal.pone.0099296. eCollection 2014.

Abstract

Interleukin (IL)-1 signaling plays an important role in inflammatory processes, but also in malignant processes. The essential downstream event in IL-1 signaling is the activation of nuclear factor (NF)-κB, which leads to the expression of several genes that are involved in cell proliferation, invasion, angiogenesis and metastasis, among them VEGF-A. As microenvironment-derived IL-1β is required for invasion and angiogenesis in malignant tumors, also in chondrosarcomas, we investigated IL-1β-induced signal transduction and VEGF-A expression in C3842 and SW1353 chondrosarcoma cells. We additionally performed in vitro angiogenesis assays and NF-κB-related gene expression analyses. Curcumin is a substance which inhibits IL-1 signaling very early by preventing the recruitment of IL-1 receptor associated kinase (IRAK) to the IL-1 receptor. We demonstrate that IL-1 signaling and VEGF-A expression are blocked by Curcumin in chondrosarcoma cells. We further show that Curcumin blocks IL-1β-induced angiogenesis and NF-κB-related gene expression. We suppose that IL-1 blockade is an additional treatment option in chondrosarcoma, either by Curcumin, its derivatives or other IL-1 blocking agents.

MeSH terms

  • Cell Line, Tumor
  • Chondrosarcoma / metabolism
  • Chondrosarcoma / pathology
  • Curcumin / pharmacology*
  • Gene Expression Regulation / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / metabolism*
  • Interleukin-1 / pharmacology
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • NF-kappa B / metabolism
  • Neovascularization, Physiologic / drug effects
  • Phosphorylation / drug effects
  • Receptors, Interleukin-1 / metabolism
  • Signal Transduction / drug effects*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Interleukin-1
  • NF-kappa B
  • Receptors, Interleukin-1
  • Vascular Endothelial Growth Factor A
  • Interleukin-1 Receptor-Associated Kinases
  • Curcumin

Grants and funding

The authors have no support or funding to report.