DNA chip analysis of comprehensive food function: inhibition of angiogenesis and telomerase activity with unsaturated vitamin E, tocotrienol.
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, delta-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.
Nakagawa
Kiyotaka
K
Food & Biodynamic Chemistry Laboratory, Graduate School of Life Science and Agriculture, Tohoku University, Sendai 981-8555, Japan.
Eitsuka
Takahiro
T
Inokuchi
Hitoshi
H
Miyazawa
Teruo
T
D000482:Allantois / Q000098:blood supply; D000818:Animals; D001011:Aorta; D002417:Cattle; D002455:Cell Division; D002460:Cell Line; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005504:Food Analysis; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D019098:Telomerase / Q000037:antagonists & inhibitors*; D024508:Tocotrienols / Q000032:analysis* / Q000494:pharmacology*; D014471:Umbilical Veins
D024508:Tocotrienols; D012313:RNA; D019098:Telomerase