Effect of EGCG, a major component of green tea, on the expression of Ets-1, c-Fos, and c-Jun during angiogenesis in vitro.
ABSTRACT In this study, we used rat aortic endothelial cells and human umbilical vein endothelial cells growing in collagen gel as a model system to study the tea catechin, (-)-epigallocatechin (EGCG), on the differential expression of transcription factors, Ets-1, c-Fos, and c-Jun during endothelial morphogenesis in vitro. Cells growing in collagen gel from 0 to 2 h remained spherical. After 6 h, the cells became elongated and underwent morphogenesis. At 24 h, cells started to organize to form capillary-like tubular structures. At 48 h, most cells in the gel formed a network of branching and tubular structures. Immunohistochemistry and immunofluorescence microscopy showed that the reaction products of Ets-1, c-Fos, and c-Jun presented predominantly in the nucleus. No reaction products appeared in the cells that were organized to form capillary-like tubular structures. After adding EGCG to the collagen gel, cells became elongated in the first 6 h and then remained quiescent. No tubular structure was formed. Western blotting showed that the levels of Ets-1, c-Fos, and c-Jun reached the highest levels at 12-24 h, decreasing to the basal level at 48 h. After adding EGCG to the collagen gel, levels were lower than for the non-EGCG-treated groups. These results indicated that the morphogenesis of endothelial cells in collagen gel was inhibited by EGCG through the down-regulation of Ets-1, c-Fos, and c-Jun.
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ABSTRACT: Angiogenesis, the formation of new blood vessels from preexisting vascular network is a driving force of organ development in ontogeny, is necessary for ovulation and hair growth, and is prerequisite for proper wound healing. It is also a critical mechanism of numerous diseases, the most important of which are cancer and atherosclerosis. Therefore, modulation of angiogenesis is considered as therapeutic strategies of great importance for human health. Numerous bioactive plant compounds, often referred to as nutraceuticals are recently tested for the potential clinical applications. Among the most frequently studied are resveratrol, a polyphenol present in red-wine and grape-seed, epigallocatechin-3-gallate (EGCG) from green tea and curcumin from Curcuma longa. It is also possible that components of other plants, including the constituents of local food diet may find application for modulation of angiogenesis, provided that their effectiveness will be confirmed in controlled, scientifically validated trials.Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 04/2005; 56 Suppl 1:51-67. · 2.72 Impact Factor
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ABSTRACT: Green tea polyphenol, (-)-epigallocatechin-3-gallate, has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The aim of this study was to investigate the possibility of (-)-epigallocatechin-3-gallate as a novel therapeutic agent for the patients with B-cell malignancies including multiple myeloma. We investigated the effects of (-)-epigallocatechin-3-gallate on the induction of apoptosis in HS-sultan as well as myeloma cells in vitro and further examined the molecular mechanisms of (-)-epigallocatechin-3-gallate-induced apoptosis. (-)-Epigallocatechin-3-gallate rapidly induced apoptotic cell death in various malignant B-cell lines in a dose- and time-dependent manner. (-)-Epigallocatechin-3-gallate-induced apoptosis was in association with the loss of mitochondrial transmembrane potentials (Deltapsim); the release of cytochrome c, Smac/DIABLO, and AIF from mitochondria into the cytosol; and the activation of caspase-3 and caspase-9. Elevation of intracellular reactive oxygen species (ROS) production was also shown during (-)-epigallocatechin-3-gallate-induced apoptosis of HS-sultan and RPMI8226 cells as well as fresh myeloma cells. Antioxidant, catalase, and Mn superoxide dismutase significantly reduced ROS production and (-)-epigallocatechin-3-gallate-induced apoptosis, suggesting that ROS plays a key role in (-)-epigallocatechin-3-gallate-induced apoptosis in B cells. Furthermore, a combination with arsenic trioxide (As2O3) and (-)-epigallocatechin-3-gallate significantly enhanced induction of apoptosis compared with As2O3 alone via decreased intracellular reduced glutathione levels and increased production of ROS. (-)-Epigallocatechin-3-gallate has potential as a novel therapeutic agent for patients with B-cell malignancies including multiple myeloma via induction of apoptosis mediated by modification of the redox system. In addition, (-)-epigallocatechin-3-gallate enhanced As2O3-induced apoptosis in human multiple myeloma cells.Clinical Cancer Research 09/2005; 11(16):6040-9. DOI:10.1158/1078-0432.CCR-04-2273 · 8.19 Impact Factor
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ABSTRACT: The global prevalence of obesity has increased considerably in the last decade. Tools for obesity management, including caffeine, ephedrine, capsaicin, and green tea have been proposed as strategies for weight loss and weight maintenance, since they may increase energy expenditure and have been proposed to counteract the decrease in metabolic rate that is present during weight loss. A combination of caffeine and ephedrine has shown to be effective in long-term weight management, likely due to different mechanisms that may operate synergistically, e.g., respectively inhibiting the phosphodiesterase-induced degradation of cAMP and enhancing the sympathetic release of catecholamines. However, adverse effects of ephedrine prevent the feasibility of this approach. Capsaicin has been shown to be effective, yet when it is used clinically it requires a strong compliance to a certain dosage, that has not been shown to be feasible yet. Also positive effects on body-weight management have been shown using green tea mixtures. Green tea, by containing both tea catechins and caffeine, may act through inhibition of catechol O-methyl-transferase, and inhibition of phosphodiesterase. Here, the mechanisms may also operate synergistically. In addition, tea catechins have antiangiogenic properties that may prevent development of overweight and obesity. Furthermore, the sympathetic nervous system is involved in the regulation of lipolysis, and the sympathetic innervation of white adipose tissue may play an important role in the regulation of total body fat in general.AJP Regulatory Integrative and Comparative Physiology 02/2007; 292(1):R77-85. DOI:10.1152/ajpregu.00832.2005 · 3.53 Impact Factor