title: Canstatin-N fragment inhibits in vitro endothelial cell proliferation and suppresses in vivo tumor growth.
abstract: Type IV collagen is one of the components of vascular basement involved in regulation of angiogenesis. Canstatin, the non-collagenous 1 (NC1) domain of alpha2 chain of type IV collagen, was identified as an inhibitor of angiogenesis and tumor growth by Kamphaus et al. Our previous studies showed that canstatin-N, the N-terminal 1-89 amino acid fragment of canstatin, inhibited the neovascularization in a dose-dependent manner as tested by CAM assay. In the present study, we demonstrate that canstatin-N produced in Escherichia coli specifically inhibited in vitro the proliferation of human umbilical vein endothelial cells (ECV304) and significantly induced apoptosis. The apoptosis-inducing activity of canstatin-N was much stronger than that of canstatin, indicating that the apoptosis-inducing activity of canstatin is likely located within its N-terminal 1-89 amino acid fragment. Canstatin-N also suppressed in vivo growth of B(16) murine melanoma in BALB/c mice at a dosage of 10mg/kg/day. These results suggest that canstatin-N is a useful candidate molecule for inhibition of tumor growth.
authors.affiliation: The Key Laboratory of Genetic Engineering of Ministry of Education, Department of Biochemistry, Sun Yat-sen University, Guangzhou 510275, PR China.
authors.forename: Guo-An
authors.initials: GA
authors.lastname: He
authors.forename: Jin-Xian
authors.initials: JX
authors.lastname: Luo
authors.forename: Tian-Yuan
authors.initials: TY
authors.lastname: Zhang
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Wang
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D008297:Male; D008545:Melanoma / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000254:growth & development
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D024141:Collagen Type IV; D010446:Peptide Fragments; D011994:Recombinant Proteins; C482069:constatin (1-89)