Angiogenesis and Cancer Prevention by Selenium
Abstract
Our overall aim is to understand the role of inhibition of angiogenesis by selenium (Se) in breast cancer chemoprevention. We first established the anti- angiogenesis phenomenon of chemopreventive intake of Se with data supporting an association of reduced microvessel density and decreased vascular endothelial growth factor expression with mammary cancer prevention by Se (Mol. Carcinog. 1999). We discovered a specific inhibitory effect of methylselenium on vascular endothelial expression of matrix metalloproteinase-2 and vascular endothelial growth factor by breast and prostate cancer epithelial cells (Mol. Carcinog. - 2000). Since endothelial proliferation is a critical component of the angiogenic responses, we have investigated a potent inhibitory effect of methylselenium on mitogenesis of vascular endothelial cells and established phosphatidylinositol 3- kinase as a potential target pathway for signaling G1 arrest (Cancer Res 2001, Mol Carcinog. 2002). We also developed methods for evaluating anti-angiogenic attributes (pro-angiogenic factors, mitogenesis, apoptosis, capillary differentiation etc) of Se and validated with other agents. In summary, our results support the methylselenol metabolite pool with desirable anti-angiogenic attributes in addition to inhibitory actions on cell proliferation (G1 arrest) and survival (caspase-mediated apoptosis). In total, ten publications and 3 grants (total direct $1,400,000) have resulted from this support.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA411465
Entities
People
- Junxuan Lu