1. Canstatin-N fragment inhibits in vitro endothelial cell proliferation and suppresses in vivo tumor growth.
- Author
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He GA, Luo JX, Zhang TY, Wang FY, and Li RF
- Subjects
- Angiogenesis Inhibitors pharmacology, Animals, Antineoplastic Agents pharmacology, Breast Neoplasms pathology, Breast Neoplasms physiopathology, Cell Division drug effects, Cell Line, Cell Line, Tumor, Collagen Type IV chemistry, Dose-Response Relationship, Drug, Endothelium, Vascular cytology, Fibroblasts cytology, Fibroblasts drug effects, Humans, Lung cytology, Lung drug effects, Lung growth & development, Male, Melanoma physiopathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neovascularization, Pathologic pathology, Neovascularization, Physiologic drug effects, Peptide Fragments chemistry, Protein Structure, Tertiary, Recombinant Proteins pharmacology, Umbilical Veins cytology, Umbilical Veins drug effects, Umbilical Veins growth & development, Apoptosis drug effects, Collagen Type IV pharmacology, Endothelium, Vascular drug effects, Endothelium, Vascular growth & development, Melanoma pathology, Peptide Fragments pharmacology
- 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.
- Published
- 2003
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