title: Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo.
abstract: The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interests of researchers to find novel cancer therapies aiming to inhibit angiogenesis and tumor growth. Quercetin is a flavonoid compound that widely exists in the nature. Our previous study preliminarily demonstrated that quercetin effectively inhibited human prostate cancer cell xenograft tumor growth by inhibiting angiogenesis. Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose-dependent manner; ⅱ) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); ⅲ) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; ⅳ) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Feiya
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, The Third Hospital of Nanchang, Jiangxi, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Reproductive Immunology and Pharmacology, National Research Institute for Family Planning, Beijing, P.R. China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, P.R. China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Mei
authors.affiliation: Institute of Neuroscience, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, P.R. China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Nianzeng
authors.initials: N
authors.lastname: Xing
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011794:Quercetin / Q000008:administration & dosage*; D019700:Thrombospondin 1 / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D019700:Thrombospondin 1; D011794:Quercetin