Investigational New Drugs

, Volume 30, Issue 3, pp 898–915

Inhibition of TGF-β signaling, vasculogenic mimicry and proinflammatory gene expression by isoxanthohumol

  • Annegret Serwe
  • Kristina Rudolph
  • Timm Anke
  • Gerhard Erkel
PRECLINICAL STUDIES
  • 375 Downloads

Summary

TGF-β is a multifunctional cytokine that regulates cell proliferation, differentiation, apoptosis and extracellular matrix production. Deregulation of TGF-β production or signaling has been associated with a variety of pathological processes such as cancer, metastasis, angiogenesis and fibrosis. Therefore, TGF-β signaling has emerged as an attractive target for the development of new cancer therapeutics. In a screening program of natural compounds from fungi inhibiting the TGF-β dependent expression of a reporter gene in HepG2 cells, we found that the flavone isoxanthohumol inhibited the binding of the activated Smad2/3 transcription factors to the DNA and antagonized the cellular effects of TGF-β including reporter gene activation and expression of TGF-β induced genes in HepG2 and MDA-MB-231 cells. In an in vitro angiogenesis assay, isoxanthohumol (56 μM) strongly decreased the formation of capillary-like tubules of MDA-MB-231 cells on Matrigel. In addition, we found that isoxanthohumol blocked IFN-γ, IL-4 and IL-6 dependent Jak/Stat signaling and strongly inhibited the induction of pro-inflammatory genes in MonoMac6 cells at the transcriptional level after LPS/TPA treatment.

Keywords

Isoxanthohumol TGF-β signaling Vasculogenic mimicry 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Annegret Serwe
    • 1
  • Kristina Rudolph
    • 1
  • Timm Anke
    • 2
  • Gerhard Erkel
    • 2
  1. 1.Institute of Biotechnology and Drug Research (IBWF e. V.)KaiserslauternGermany
  2. 2.Department of BiotechnologyUniversity of KaiserslauternKaiserslauternGermany

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