AUTHOR=Zhang Pan , Lai Xing , Zhu Mao-Hua , Long Mei , Liu Xue-Liang , Wang Zi-Xiang , Zhang Yifan , Guo Run-Jie , Dong Jing , Lu Qin , Sun Peng , Fang Chao , Zhao Mei TITLE=Saikosaponin A, a Triterpene Saponin, Suppresses Angiogenesis and Tumor Growth by Blocking VEGFR2-Mediated Signaling Pathway JOURNAL=Frontiers in Pharmacology VOLUME=Volume 12 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.713200 DOI=10.3389/fphar.2021.713200 ISSN=1663-9812 ABSTRACT=Saikosaponin A (SSA), a main triterpenoid saponin component from Radix Bupleurum, has been revealed to have a variety of pharmacological activities. However, whether SSA can inhibit angiogenesis, a key step for solid tumor progression, remains unknown. In this study, we demonstrated that SSA could powerfully suppress the proliferation, migration and tube formation of human umbilical vein endothelial cells. SSA also significantly inhibited angiogenesis in the models of the chick embryo chorioallantoic membrane and Matrigel plugs. Moreover, SSA was found to inhibit tumor growth in both orthotopic 4T1 breast cancer and subcutaneous HCT-15 colorectal tumor by inhibition of tumor angiogenesis. Western blot assay indicated the antiangiogenic mechanism of SSA is suppression of protein phosphorylation of VEGFR2 and the downstream protein kinase including PLCĪ³1, FAK, Src, and Akt. These observations suggested that SSA may serve as a potential drug candidate or lead compound for antiangiogenic cancer therapy.