Kochia scoparia seed extract suppresses VEGF-induced angiogenesis via modulating VEGF receptor 2 and PI3K/AKT/mTOR pathways

Abstract Context: Kochia scoparia (L.) Schrad (Amaranthaceae), known as a traditional medicine in China, Japan and Korea, is reported to have various biological activities. However, K. scoparia seed extract (KSE) functional roles on angiogenesis and prostate cancer inhibition have not been elucidated. Objective: This study elucidates the effects of KSE on vascular endothelial growth factor (VEGF)-induced angiogenesis in human umbilical vein endothelial cells (HUVECs) and inhibition of proliferation in prostate cancer cells. Materials and methods: HUVECs were treated with 10–20？μg/mL of KSE and 20–50？ng/mL of VEGF for 12–72？h. Anti-angiogenesis properties of KSE were determined by wound healing, trans-well, tube formation, rat aortic ring assay and western blotting. Prostate cancer and normal cells were incubated with 10–250？μg/mL of KSE for 24？h, and cell viability was measured by SRB assay. Phenolic compounds in KSE were analyzed using a HPLC-PDA system. Results: IC50 for cell viability of HUVECs, LNCaP, PC-3, RC-58T and RWPE-1 by KSE were 30.64, 89.25, 123.41, 141.62 and >250？μg/mL, respectively. Treatment with KSE (20？μg/mL) significantly suppressed VEGF-induced migration, invasion and capillary-like structure formation of HUVECs and microvessel sprouting from rat aortic rings. In addition, KSE down-regulated PI3K/AKT/mTOR levels and phosphorylation of VEGF receptor 2 in HUVECs. 3-OH-tyrosol (1.63？mg/g) and morin hydrate (0.17？mg/g) were identified in KSE. Conclusions: KSE inhibits angiogenesis in HUVECs as well as proliferation in human prostate cancer cells, suggesting KSE may be useful herbal medicine for preventing progression of prostate cancer and angiogenesis