1. Canstatin-N fragment inhibits in vitro endothelial cell proliferation and suppresses in vivo tumor growth
- Author
-
He, Guo-An, Luo, Jin-Xian, Zhang, Tian-Yuan, Wang, Fang-Yu, and Li, Rui-Fang
- Subjects
- *
COLLAGEN , *ANTINEOPLASTIC agents , *NEOVASCULARIZATION , *ENDOTHELINS - 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 α2 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 B16 murine melanoma in BALB/c mice at a dosage of 10 mg/kg/day. These results suggest that canstatin-N is a useful candidate molecule for inhibition of tumor growth. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF