Cultivated Orostachys japonicus extract inhibits VEGF-induced angiogenesis via regulation of VEGFR2 signaling pathway in vitro and in vivo

Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways

“…Ingredient analysis studies on quality control and standardization of the chemical constituents obtained from O. japonica are largely carried out in Korea. According to studies published until now, O. japonica has been reported to contain sterols, flavonoids, phenolic acids, and triterpenoids [ 11 ]. Twelve flavonoid compounds have been separated and identified from O. japonica , including kaempferol, quercetin, astragalin, quercitrin, isoquercitrin, cynaroside, afzelin, 3- o -a-L-rhamnosyl-7- o -13- d -glucosyl kaempferol, 3,7-di- o -13- d -glucosyl kaempferol, kaempferol 3- o -β- d -glucoside, kaempferol 3- o -β- d -galactoside, and quercetin 3- o -β- d -glucoside [ 12 , 13 ].…”

“…Activated endothelial cells for angiogenesis require a response to vascular endothelial growth factor (VEGF) secretion from tumor cells, the production of proteolytic enzymes such as matrix metalloproteinases (MMPs), migration, adhesion, and tube formation (molecular mediators of angiogenesis). First, the 70% ethanol extract of O. japonica suppressed the proliferation of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) and angiogenic sprouting from the Sprague Dawley (SD) rat aortic rings without toxicity [ 11 ]. The inhibitory actions of O. japonica against angiogenesis were consistently observed in VEGF-induced C57BL/6 mice [ 66 ] and xenograft BALB/c mice [ 52 ] implanted with prostate cancer cells by decreasing the number of infiltrating vessels into the Matrigel plug.…”

“…The inhibitory actions of O. japonica against angiogenesis were consistently observed in VEGF-induced C57BL/6 mice [ 66 ] and xenograft BALB/c mice [ 52 ] implanted with prostate cancer cells by decreasing the number of infiltrating vessels into the Matrigel plug. Next, O. japonica extract decreased the level of MMP-9 protein and elevated TIMP-1 protein expression in HUVECs, which might prevent endothelial cells from escaping from pre-existing capillaries and moving to tumor tissue [ 11 ]. In addition, the 70% methanol extract of O. japonica fermented with Aspergillus kawachii was excellent for lowering the number of migrated cells required for invasive cancer; this was observed using a wound healing assay and Transwell migration assay in Ms-1 endothelial cells via focal adhesion kinase (FAK) and Src inactivation [ 66 ].…”

“…In addition, the 70% methanol extract of O. japonica fermented with Aspergillus kawachii was excellent for lowering the number of migrated cells required for invasive cancer; this was observed using a wound healing assay and Transwell migration assay in Ms-1 endothelial cells via focal adhesion kinase (FAK) and Src inactivation [ 66 ]. Similarly, migrated cells were diminished in the presence of the 70% ethanol extract of O. japonica in VEGF-stimulated HUVECs through the blockade of FAK/Src, phosphoinositide 3-kinase (PI3K)/protein kinase B (Atk)/mammalian target of rapamycin (mTOR), and MAPK [ 11 ]. Furthermore, O. japonica improved key angiogenic processes, such as the differentiation of endothelial cells into the capillary web structure and tube formation, in Ms-1 cells and HUVECs [ 61 , 66 ] ( Table 2 ).…”

Pentapeptide AYP from Isochrysis Zhanjiangensis Exhibits Antiangiogenic Activity in HT1080 Cells and HUVECs by Suppressing Migration and Invasion In Vitro

“…Notably, VEGFR-2 has been identified as a master regulator of angiogenesis. It can directly control the angiogenic potential of endothelial cells by transducing signals that form three-dimensional (3D) blood vessels and plays an important role in the formation of tumor angiogenesis. , Therefore, the VEGFR-2 signaling pathway plays an important role in developmental processes and angiogenesis. At present, anti-VEGF drugs have been applied to prevent and treat this pathology.…”