NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway
- Chemical Genomics Laboratory, Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)
- Translation Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506 (Japan)
Nuclear factor-{kappa}B (NF-{kappa}B) 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-{kappa}B 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-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.
- OSTI ID:
- 22202332
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 391; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Sensitization of TNF-induced cytotoxicity in lung cancer cells by concurrent suppression of the NF-{kappa}B and Akt pathways
Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription