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|標題:||Vitamin E and rutin synergistically inhibit expression of vascular endothelial growth factor through down-regulation of binding activity of activator protein-1 in human promyelocytic leukemia (HL-60) cells||作者:||Chuang, C.H.
|關鍵字:||Activator protein-1;Human promyelocytic leukemia;Rutin;Vitamin E;Vascular endothelial growth factor;acute myeloid-leukemia;factor-i receptor;human tumor-cells;alpha-tocopherol;oxidative stress;lung-cancer;cardiovascular-disease;lipid-peroxidation;tyrosine kinase;messenger-rna||Project:||Chemico-Biological Interactions||期刊/報告no：:||Chemico-Biological Interactions, Volume 183, Issue 3, Page(s) 434-441.||摘要:||
Reactive oxygen species (ROS) are strong inducers of the angiogenic hormone vascular endothelial growth factor (VEGF). Although, rutin (R) in combination with vitamin E (VE) has been shown to synergistically inhibit oxidative damage, it is unclear whether the combination of R and VE (R+VE) inhibits VEGF secretion in tumor cells. Using a human promyelocytic leukemia (HL-60) cell line, we showed that R in combination with VE synergistically decreased the expressions of VEGF protein and mRNA. We also demonstrated that R + VE significantly decreased the binding capacity of nuclear factor-activator protein-1 (AP-1) to the VEGF gene promoter and decreased the expression of c-Jun protein. Furthermore, we demonstrated that R + VE synergistically reduced insulin receptor substrate-1 (IRS-1) protein expression in HL-60 cells. The decrease of ROS was only partially associated with the decrease of VEGF secreted (r(2) = 0.12, P= 0.083). Thus, the present results indicate that R in combination with VE attenuates VEGF expression in HL-60 cells and that this effect is mediated by a decreased binding activity of AP-1 through down-regulation of protein expression of insulin-like growth factor 1 receptor (IGFI-R)/IRS-1. while the antioxidant activity of R + VE appears to play a minor role. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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