Jujuboside B suppresses angiogenesis and tumor growth via blocking VEGFR2 signaling pathway
Pan Zhang,
Xing Lai,
Mao-Hua Zhu,
Jiangpei Shi,
Hong Pan,
Yanhu Huang,
Run-Jie Guo,
Qin Lu,
Chao Fang,
Mei Zhao
Affiliations
Pan Zhang
Department of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China
Xing Lai
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China
Mao-Hua Zhu
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China
Jiangpei Shi
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China
Hong Pan
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China; Key Laboratory of Basic Pharmacology of Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563003, China
Yanhu Huang
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China
Run-Jie Guo
Department of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China
Qin Lu
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China
Chao Fang
Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China; Key Laboratory of Basic Pharmacology of Ministry of Education & Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563003, China; Corresponding author. Hongqiao International Institute of Medicine, Tongren Hospital and State Key Laboratory of Systems Medicine for Cancer, Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 200025, China.
Mei Zhao
Department of Pharmacy, Shanghai University of Medicine & Health Sciences, Shanghai, 201318, China; Corresponding author.
Jujuboside B (JuB), one of the main active triterpenoid saponins from the traditional Chinese medicine Ziziphus jujuba, possesses a wide range of pharmacological activities. However, it is unknown whether JuB can inhibit tumor angiogenesis, a crucial step in solid tumor growth. In this study, we found that JuB significantly inhibited the proliferation, migration, and tube formation of human umbilical vein endothelial cells in a dose-dependent manner. JuB also suppressed angiogenesis in chick embryo chorioallantoic membranes and Matrigel plugs. Moreover, through angiogenesis inhibition, JuB delayed the growth of human HCT-15 colorectal cancer xenograft in mice. Western blot assay demonstrated that JuB inhibited the phosphorylation of VEGFR2 and its key downstream protein kinases, such as Akt, FAK, Src, and PLCγ1. In conclusion, the antiangiogenic potency and molecular mechanism of JuB are revealed for the first time, indicating that this triterpene saponin may be further explored as a potential drug candidate or lead compound for antiangiogenic cancer therapy.
