NBBA, a synthetic small molecule, inhibits TNF-alpha-induced angiogenesis by suppressing the NF-kappaB signaling

Nam Hee Kim1, Hye Jin Jung, Futoshi Shibasaki

  • 1Chemical Genomics Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.

Insights

A novel small molecule, NBBA, effectively inhibits angiogenesis by targeting the NF-kappaB pathway. It suppresses endothelial cell growth, invasion, and in vivo neovascularization, offering a new therapeutic strategy for cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Nuclear factor-kappaB (NF-kappaB) is a key transcription factor implicated in cancer development.
  • NF-kappaB regulates genes involved in angiogenesis and tumorigenesis.
  • Targeting NF-kappaB is a promising strategy for anti-cancer therapies.

Purpose of the Study:

  • To introduce (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene)propan-2-amine oxide (NBBA) as a novel small molecule.
  • To investigate NBBA's anti-angiogenic properties and its mechanism of action.
  • To evaluate NBBA's effect on the NF-kappaB signaling pathway.

Main Methods:

  • NBBA's effect on human umbilical vein endothelial cells (HUVECs) and cancer cell lines was assessed.
  • In vitro assays measured TNF-alpha-induced HUVEC tube formation and invasion.
  • In vivo neovascularization was evaluated using the chick embryo chorioallantoic membrane model.
  • The impact of NBBA on TNF-alpha-induced NF-kappaB transcription activity and related signaling pathways was analyzed.

Main Results:

  • NBBA demonstrated significant growth inhibition on HUVECs.
  • NBBA suppressed TNF-alpha-induced HUVEC tube formation and invasion.
  • In vivo studies showed NBBA inhibited neovascularization in chick embryos.
  • NBBA effectively suppressed TNF-alpha-induced NF-kappaB transcription activity by inhibiting c-Jun N-terminal kinase phosphorylation.
  • NBBA reduced the transcription of NF-kappaB target genes, including IL-8, IL-1alpha, and EGF.

Conclusions:

  • NBBA is a potent anti-angiogenic small molecule.
  • NBBA exerts its anti-angiogenic effects by targeting the NF-kappaB signaling pathway.
  • NBBA represents a potential therapeutic agent for angiogenesis-dependent diseases, including cancer.

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