title: Investigation of the anti-angiogenesis effects induced by deoxypodophyllotoxin-5-FU conjugate C069 against HUVE cells.
abstract: We have found that the deoxypodophyllotoxin-5-fluorouracil conjugate, 4'-O-demethyl-4-deoxyppodophyllotoxin-4'-yl 4-((6-(2-(5-fluorouracil-yl)acetamido) hexyl)amino)-4-oxobutanoate (C069), possessed superior cytotoxicities and less toxicity compared with etoposide. In this paper, the anti-angiogenic and vascular disrupting activities of C069 were examined with several in vitro and in vivo models. First, we demonstrated that C069 significantly inhibited the proliferation, migration, tube formation and disrupted the formed tube-like structures of HUVE cells, and inhibited angiogenesis in chicken chorioallantoic membrane assay. Furthermore, we found that C069 inhibited tube formation of HUVE cells by down-regulating the MMP-2, MMP-9, and phosphorylation of Akt and β-catenin. These results provided the initial evidence that C069 exerts potent anti-angiogenic and vascular disrupting effects.
authors.affiliation: Department of Medicinal, Second Clinical Hospital of Northwest University for Nationalities & Second Provincial People's Hospital, Lanzhou 730000, PR China. Electronic address: xiangr04@qq.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Guan
authors.affiliation: Experimental Center of Medicine, General Hospital of Lanzhou Military Command, Lanzhou 730050, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hui
authors.affiliation: Department of Medicinal, Second Clinical Hospital of Northwest University for Nationalities & Second Provincial People's Hospital, Lanzhou 730000, PR China.
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, PR China. Electronic address: chenshw@lzu.edu.cn.
authors.forename: Shi-Wu
authors.initials: SW
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal; D005047:Etoposide / Q000633:toxicity; D005472:Fluorouracil / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C000611971:4'-O-demethyl-4-deoxypodophyllotoxin-4'-yl 4-((6-(2-(5-fluorouracil-yl)acetamido)hexyl)amino)-4-oxobutanoate; D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D051176:beta Catenin; C014451:deoxypodophyllotoxin; D005047:Etoposide; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011034:Podophyllotoxin; D005472:Fluorouracil
keywords: 5-Fluorouracil; Angiogenesis; Migration; Podophyllotoxin; Vascular disrupting effects