Lupeol and stigmasterol suppress tumor angiogenesis and inhibit cholangiocarcinoma growth in mice via downregulation of tumor necrosis factor-α

• DOI: 10.1371/journal.pone.0189628
• Publication Date: 2017-12-12T14:08:37Z
• Authors: Thaned Kangsamaksin; Supattra Chaithon...; Chanida Wootthich...; Rattanavinan Hanc...; Chayada Tangshewi...; Jisnuson Svasti
• Keywords: Lupeol; Stigmasterol; DU145; CD31

Lupeol and stigmasterol, major phytosterols in various herbal plants, possess anti-inflammatory activities have been proposed as candidates for anti-cancer agents, but their molecular mechanisms are still unclear. Here, we investigated the effects of lupeol stigmasterol on tumor endothelial cells vitro vivo. Our results demonstrated that suppressed cell viability, migration, morphogenesis human umbilical vein (HUVECs) not cholangiocarcinoma (CCA) cells. Expression analyses showed treatment both compounds significantly reduced transcript level necrosis factor-α (TNF-α), Western blot further revealed a decrease downstream effector levels VEGFR-2 signaling, including phosphorylated forms Src, Akt, PCL, FAK, which were rescued by TNF-α treatment. In vivo, disrupted angiogenesis growth CCA xenografts. Immunohistochemical confirmed CD31-positive vessel content macrophage recruitment upon These findings indicate effectively target suppress attractive tumors.