2. Academic Validation
  3. Pirfenidone inhibits TGF-beta expression in malignant glioma cells

Pirfenidone inhibits TGF-beta expression in malignant glioma cells

  • Biochem Biophys Res Commun. 2007 Mar 9;354(2):542-7. doi: 10.1016/j.bbrc.2007.01.012.
Isabel Burghardt 1,  Felix Tritschler,  Christiane A Opitz,  Brigitte Frank,  Michael Weller,  Wolfgang Wick
Affiliations

Affiliation

  • 1 Laboratory of Molecular Neuro-Oncology, Department of General Neurology and Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, D-72076, Tübingen, Germany.
PMID: 17234158 DOI: 10.1016/j.bbrc.2007.01.012
Abstract

Due to its immunosuppressive properties, the cytokine transforming growth factor (TGF)-beta has become a promising target in the experimental treatment of human malignant gliomas. Here, we report that the antifibrotic drug 5-methyl-1-phenyl-2-(1H)-pyridone (pirfenidone, PFD) elicits growth-inhibitory effects and reduces TGF-beta2 protein levels in human glioma cell lines. This reduction in TGF-beta2 is biologically relevant since PFD treatment reduces the growth inhibition of TGF-beta-sensitive CCL-64 cells mediated by conditioned media of glioma cells. The downregulation of TGF-beta is mediated at multiple levels. PFD leads to a reduction of TGF-beta2 mRNA levels and of the mature TGF-beta2 protein due to decreased expression and direct inhibition of the TGF-beta pro-protein convertase Furin. In addition, PFD reduces the protein levels of the matrix metalloproteinase (MMP)-11, a TGF-beta target gene and Furin substrate involved in carcinogenesis. These data define PFD or PFD-related agents as promising agents for human cancers associated with enhanced TGF-beta activity.

Figures
Products