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Updated: Jun 17, 2026

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
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.
Abstract:
Nuclear factor-kappaB (NF-kappaB) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene)propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-kappaB activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-alpha)-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effect of NBBA on TNF-alpha-induced NF-kappaB transcription activity was investigated. NBBA suppressed TNF-alpha-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-kappaB and its target genes, including interleukin-8, interleukin-1alpha, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-kappaB signaling pathway.
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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