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 |
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| Authors: | Cheng-Hung Chuang Chin-Shiu Huang Miao-Lin Hu |
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| Affiliation: | 1. Clinic for Endocrinology, Diabetes and Metabolic Diseases, Genetic Laboratory, Clinical Center of Serbia, Belgrade, Serbia;2. Laboratory of Experimental Hematology, Institute for Medical Research, University of Belgrade, Belgrade, Serbia;;3. Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA;1. Departments of Medical Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea;2. Department of Biomedical Laboratory Science, College of Medical Sciences, SoonChunHyang University, Chungnam, Asan 336-745, Republic of Korea;3. Aptabio Therapeutics Inc., Kyunggi-do, Yong-in city 446-908, Republic of Korea;4. Department of Chemistry and MedChem Program, Life Sciences Institute, National University of Singapore, 3 Science Drive 3, Singapore, 117543;5. Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium (SBIC), 11 Biopolis Way, #02-02 Helios, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore, 138667;6. Department of Imaging, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea;1. Institute for Coastal Marine Environment (IAMC), National Research Council (CNR), Messina, Italy;2. Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”, National Research Council (CNR), Napoli, Italy;3. Interuniversity Consortium of Structural and Systems Biology, Roma, Italy |
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| Abstract: | 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 (r2 = 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 (IGF1-R)/IRS-1, while the antioxidant activity of R + VE appears to play a minor role. |
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