Canstatin-N fragment inhibits in vitro endothelial cell proliferation and suppresses in vivo tumor growth.
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.
He
Guo-An
GA
The Key Laboratory of Genetic Engineering of Ministry of Education, Department of Biochemistry, Sun Yat-sen University, Guangzhou 510275, PR China.
Luo
Jin-Xian
JX
Zhang
Tian-Yuan
TY
Wang
Fang-Yu
FY
Li
Rui-Fang
RF
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
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D024141:Collagen Type IV; D010446:Peptide Fragments; D011994:Recombinant Proteins; C482069:constatin (1-89)