Nuclear factor-κB (NF-κB) 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)propa n-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-κB 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-α)-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-α-induced NF-κB transcription activity was investigated. NBBA suppressed TNF-α-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-κB and its target genes, including interleukin-8, interleukin-1α, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-κB signaling pathway.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2010 Jan 15|
Bibliographical noteFunding Information:
This study was supported by grants from the Translational Research Center for Protein Function Control, Korea Basic Science Institute (KBSI) , and the Brain Korea 21 Project, KRF . We thank Dr. Jong Shin Yoo for his valuable comments and the Korea Basic Science Institute (KBSI) for technical support.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology