Abstract: Inhibition of angiogenesis and telomerase activity with vitamin E
compounds, especially for tocotrienol (T3), has been investigated. Nutrigenomic
tools have been used for elucidating the bioactive mechanisms of T3. In the
cell culture experiments, T3 reduced the vascular endothelial growth factor
(VEGF)-stimulated tube formation by human umbilical vein endothelial cells
(HUVEC). Among T3 isomers, δ-T3 appeared the highest
activity. The T3 inhibited the new blood vessels formation on the growing chick
embryo chorioallantoic membrane (CAM assay for an in vivo model of
angiogenesis). In contrast, tocopherol did not. The findings suggested that the
T3 has potential use for reducing angiogenic disorder. DNA chip analysis
revealed that T3 specifically down-regulates the expression of VEGF receptor
(VEGFR) in endothelial cells. It is well-known that VEGF regulates angiogenesis
by binding to VEGFR. Therefore, T3 could block the intracellular signaling of
VEGF via down-regulation of VEGFR, which resulted in the inhibition of
angiogenesis. On the other hand, DNA chip analysis also revealed that T3
down-regulates the expression of protein kinase C (PKC) in the cultured HUVEC.
Since PKC is involved with the control of telomerase activity, T3 has potential
to act as anti-telomerase inhibitor via PKC inhibition. In this manner, DNA
chip technology provides efficient access to genetic information regarding food
function and its mechanism.
Keywords: tocotienol, anti-angiogenesis, telomerase inhibition, nutrigenomics, DNA chip
Journal: BioFactors, vol. 21, no. 1-4, pp. 5-10, 2004
