Angiogenesis and Cancer Prevention by Selenium
Final rept. 15 May 1999-14 May 2002
AMC CANCER RESEARCH CENTER DENVER CO
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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.
- Anatomy and Physiology
- Medicine and Medical Research