SB-431542, a small molecule transforming growth factor-beta-receptor antagonist, inhibits human glioma cell line proliferation and motility.

Journal Article (Journal Article)

Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that promotes malignant glioma invasion, angiogenesis, and immunosuppression. Antisense oligonucleotide suppression of TGF-beta(2) ligand expression has shown promise in preclinical and clinical studies but at least two ligands mediate the effects of TGF-beta in gliomas. Therefore, we examined the effects of SB-431542, a novel, small molecule inhibitor of the type I TGF-beta receptor, on a panel of human malignant glioma cell lines. SB-431542 blocked the phosphorylation and nuclear translocation of the SMADs, intracellular mediators of TGF-beta signaling, with decreased TGF-beta-mediated transcription. Furthermore, SB-431542 inhibited the expression of two critical effectors of TGF-beta-vascular endothelial growth factor and plasminogen activator inhibitor-1. SB-431542 treatment of glioma cultures inhibited proliferation, TGF-beta-mediated morphologic changes, and cellular motility. Together, our results suggest that small molecule inhibitors of TGF-beta receptors may offer a novel therapy for malignant gliomas by reducing cell proliferation, angiogenesis, and motility.

Full Text

Duke Authors

Cited Authors

  • Hjelmeland, MD; Hjelmeland, AB; Sathornsumetee, S; Reese, ED; Herbstreith, MH; Laping, NJ; Friedman, HS; Bigner, DD; Wang, X-F; Rich, JN

Published Date

  • June 2004

Published In

Volume / Issue

  • 3 / 6

Start / End Page

  • 737 - 745

PubMed ID

  • 15210860

International Standard Serial Number (ISSN)

  • 1535-7163


  • eng

Conference Location

  • United States