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Antiangiogenic
activity of selenium in cancer chemoprevention: metabolite-specific effects
Lu J,
Jiang C
AMC
Cancer Research Center, Denver, CO 80214, USA. luj@amc.org
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.
PMID:
11799926 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11799926&dopt=Abstract
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