Antiangiogenic activity of selenium in cancer chemoprevention: metabolite-specific effects.
We review recent data that support a potential antiangiogenic effect of selenium (Se) in the chemoprevention of cancer and data that contrast two pools of Se metabolites, namely, methylselenol vs. hydrogen selenide, that differentially affect proteins and cellular processes crucial to tumor angiogenesis regulation. With regard to tumor angiogenesis, the chemopreventive effect of increased Se intake on chemically induced mammary carcinogenesis has been associated with reduced intratumoral microvessel density and an inhibition of the expression of vascular endothelial growth factor. The in vitro data show that monomethyl Se potently inhibits cell cycle progression of vascular endothelial cells to the S phase, endothelial expression of matrix metalloproteinase-2, and cancer epithelial expression of vascular endothelial growth factor with concentrations giving half-maximal inhibition that are within the plasma range of Se in US adults. The methyl Se-specific activities may therefore be physiologically pertinent for angiogenic switch regulation in early lesions in vivo in the context of cancer chemoprevention, which aims at retarding and blocking the growth and progression of early lesions. We argue for the antiangiogenic action of Se, especially the methyl Se pool of metabolites, as a primary mechanism for preventing avascular lesion growth. Contrary to the currently held paradigm, we speculate that there is a potential role for selenoproteins in regulating the growth and fate of transformed epithelial cells.
Lu
J
J
AMC Cancer Research Center, Denver, CO 80214, USA. luj@amc.org
Jiang
C
C
D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism* / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000517:prevention & control; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D012643:Selenium / Q000378:metabolism* / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D012643:Selenium