Baicalein reduces angiogenesis in the inflammatory microenvironment via inhibiting the expression of AP-1.
Increasing clinical and experimental studies have demonstrated that refractory chronic inflammation will result in malignant tumor and anti-angiogenic therapy may be an effective way to thwart the progression. Baicalein, one of the major active flavanoids found in Scutellaria baicalensis Georgi, has been exhibited potent anti-inflammation and anti-tumor effects by reducing angiogenesis. However, the exact mechanism of baicalein on endothelial cells in inflammatory microenvironment was not clear yet. Here, we investigated the anti-angiogenic effect of baicalein by incubating human umbilical vein endothelial cells (HUVECs) with THP-1 conditioned medium in vitro. The tube formation of HUVECs and microvessel outgrowth of rat aorta were attenuated, as well as the number of newly formed blood vessels in chicken chorioallantoic membrane (CAM) was reduced by baicalein. This anti-angiogenic effect was mainly on account of the inhibited motility, migration and invasion of HUVECs. In addition, mechanistic studies showed that baicalein could bind to AP-1 directly and the expression of c-Jun and c-Fos in HUVECs was reduced, accompanied by their increased proteasomal degradation. Besides, baicalein suppressed the nuclear translation, heterodimer formation and DNA binding affinity of c-Jun and c-Fos. What's more, the anti-angiogenic effect of baicalein was further confirmed by matrigel plug assay in vivo. Taken together, our study demonstrated that baicalein could exert its anti-angiogenic effect in the inflammation microenvironment via inhibiting the transcriptional activity of AP-1, which suggested that baicalein might be an alternative treatment against refractory chronic inflammation.
['Huang|Yujie|Y|', 'Miao|Zhaorui|Z|', 'Hu|Yang|Y|', 'Yuan|Yang|Y|', 'Zhou|Yuxin|Y|', 'Wei|Libin|L|', 'Zhao|Kai|K|', 'Guo|Qinglong|Q|', 'Lu|Na|N|']
D021581:Active Transport, Cell Nucleus D000818:Animals D002460:Cell Line D002465:Cell Movement D049109:Cell Proliferation D002470:Cell Survival D002642:Chick Embryo D044950:Flavanones D015972:Gene Expression Regulation, Neoplastic D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D051379:Mice D009389:Neovascularization, Pathologic D011485:Protein Binding D051381:Rats D015398:Signal Transduction D018808:Transcription Factor AP-1 D059016:Tumor Microenvironment
baicalein angiogenesis inflammatory AP-1