Uptake of resveratrol and role of resveratrol-targeting protein, quinone reductase 2, in normally cultured human prostate cells
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Resveratrol 是拥护对许多人的癌症类型举办 chemopreventive 活动的饮食的多酚。我们首先报导 resveratrol 显著地减少雄激素依赖者和荷尔蒙倔强的前列腺癌症房间的增长。然而，特别地关于它的举起， subcellular 分发和细胞内部的目标，在上皮的正常前列腺和 stromal 房间的 resveratrol 的效果没被调查。在前列腺房间在可接近性和 resveratrol 的细胞的布置上推进知识，[ 3H ] resveratrol ，进 subcellular 分隔空间的房间摘录的分别，西方的污点分析， resveratrol 亲密关系列层析和流动 cytometry 被用来在通常有教养的前列腺 stromal ( PrSCs )和上皮的房间( PrECs )学习举起和 resveratrol 的细胞内部的分发。为有 resveratrol 的 2 天的 PrSCs 和 PrECs 的预告的处理调制了它的举起并且有选择地增加了它的分发到膜和细胞器分隔空间。Resveratrol 亲密关系列层析研究显示出以前识别的指向 resveratrol 蛋白质的微分表示， quinone reductase 2 (QR2 ) ，在 PrSCs 和 PrECs。比较对待 resveratrol 、未经治疗的 PrSCs 的流动 cytometric 分析在在房间周期的 S 和 G2/M-phases 的 G1 阶段和伴随物增加显示出大减少。这些结果建议 resveratrol 由影响房间周期阶段分发压制 PrSC 增长，它可以由 QR2 包含参予。Cite
Gaucher disease (GD) is one of the most common lysosomal storage disorders and is caused by an inherited deficiency in glucocerebrosidase. Resveratrol is a phytoalexin that has many beneficial activities, including anti-oxidant, anti-apoptotic, and neuroprotective effects. The aim of this study was to determine if resveratrol has a therapeutic effect on primary fibroblast cells derived from a patient with type II GD. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine the effect of resveratrol on cell viability. The expression patterns of apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax), caspase-3, acetyl-coenzyme A acetyltransferase 1 (ACAT1), E3-binding protein (E3BP), and citrate synthase (CS) were evaluated by Western blotting to characterize the effect of resveratrol treatment on GD cells. TLC was performed to determine glucosylceramide levels in resveratrol-treated GD cells. Resveratrol increased GD cell viability compared to untreated control cells. Further, resveratrol treatment dose-dependently decreased the apoptotic factors AIF, Bax, and cleaved caspase-3 levels, whereas ACAT1, E3BP, and CS expression dose-dependently increased. TLC analysis showed reduced levels of intracellular glucosylceramides in resveratrol-treated GD cells. These findings demonstrate that resveratrol can reduce cellular stress resulting from glucosylceramide accumulation, and suggest that resveratrol should be studied further as a novel therapeutic agent for GD.
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Dietary resveratrol is metabolically transformed in vivo by the intestine and liver to produce resveratrol glucuronides and sulfates in humans. Little is known about the anticancer activities of these metabolic products. The majority of in vitro studies have investigated effects of resveratrol aglycone at supraphysiological levels. Physiological levels of resveratrol-3-O-glucuronide, resveratrol-4′-O-glucuronide, and resveratrol-3-O-sulfate, the major in vivo metabolites of dietary resveratrol, were evaluated as anticancer agents against Jurkat T leukemia cells. Propidium iodide was use to measure cell death and changes in cell cycle, and the mitochondrial membrane dye JC-1 was used to measure changes in mitochondrial membrane potential by flow cytometry. PKH67 was used to evaluate changes in proliferation of the cells by flow cytometry. Jurkat cells were exposed to 0, 2.5, 5, 10, 15, and 20 μM of each resveratrol metabolite, which are concentrations achievable in vivo. None of the resveratrol metabolites were able to kill Jurkat T leukemia cells or alter cell cycle or proliferation at these concentrations. Only resveratrol-3-O-sulfate induced depolarization of mitochondrial membranes but without induction of cell death. These results suggest that the in vivo transformation of resveratrol to these glucuronide and sulfate metabolites renders these agents ineffective against T leukemia cells.
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Resveratrol is a plant-derived polyphenol with chemotherapeutic properties in animal cancer models and many biochemical effects in vitro. Its bioavailability is low and raises the possibility that the metabolites of resveratrol have biological effects. Here we investigate the actions of resveratrol 3-O-D-glucuronide, resveratrol 4-O-D-glucuronide, and resveratrol 3-O-Dsulfate on the growth of colon cancer cells in vitro.The growth of Caco-2, HCT-116, and CCL-228 cells was measured using the neutral red and MTT assays. Resveratrol and each metabolite inhibited cell growth with IC50 values of 9.8–31 μM. Resveratrol caused S phase arrest in all three cell lines. Resveratrol 3-O-D-glucuronide and resveratrol 4-O-D-glucuronide caused G1 arrest in CCL-228 and Caco-2 cells. Resveratrol 3-O-D-sulfate had no effect on cell cycle. Growth inhibition was reversed by an inhibitor of AMP-activated protein kinase (compound C) or an adenosine A3 receptor antagonist (MRS1191). The A3 receptor agonist 2Cl-IB-MECA inhibited growth and A3 receptors were detected in all cell lines. The resveratrol glucuronides also reduced cyclin D1 levels but at higher concentrations than in growth experiments and generally did not increase phosphorylated AMP-activated protein kinase.Resveratrol glucuronides inhibit cell growth by G1 arrest and cyclin D1 depletion, and our results strongly suggest a role for A3 adenosine receptors in this inhibition.
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Resveratrol is a natural polyphenol that possesses various beneficial properties, such as anti‐inflammatory, anti‐oxidant, and neuroprotective effects. This study evaluated the potential therapeutic effects of resveratrol on primary fibroblasts derived from a patient with Gaucher disease. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays were carried out to determine whether resveratrol affects cell survival. Changes in the expression levels of apoptosis‐inducing factor (AIF), Bax, cleaved caspase‐3, acetyl‐coenzyme A acetyltransferase 1 (ACAT1), E3‐binding protein (E3BP), and citrate synthase (CS) were determined by western immunoblot to characterize the effect of resveratrol treatment on Gaucher disease cells. Intracellular glucosylceramide levels in resveratrol‐treated patient cells were determined by thin‐layer chromatography (TLC). Resveratrol significantly increased the viability of patient cells in comparison with that of control cells. After exposure to resveratrol, expression levels of the apoptotic factors AIF, Bax, and cleaved caspase‐3 dose‐dependently decreased, while those of ACAT1, E3BP, and CS dose‐dependently increased. TLC showed a significant decrease in glucosylceramide levels in patient cells treated with resveratrol. These findings demonstrate that resveratrol can reduce apoptotic events and glucosylceramide levels in Gaucher disease cells, and that it merits further research as a possible therapeutic compound. Copyright © 2015 John Wiley & Sons, Ltd.
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Abstract Background Resveratrol is a natural polyphenolic compound and its anticancer effect has been receiving considerable attention. Previous studies showed that resveratrol could inhibited the growth of human gastric carcinoma cells and apoptosis induction was an important mechanism. However, whether mitochondrial pathway was involved in resveratrol‐induced apoptosis in human gastric cancer was not very clear. Methods The cells were examined by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay, Annexin V/PI staining assay, mitochondrial membrane depolarization, cell morphological assessment, cytochrome c release assay, and Western blotting assay. Results In this study, we found that resveratrol induced apoptosis in human gastric carcinoma SGC‐7901 cells. Cleaved PARP was observed and caspase‐3 was activated by resveratrol. Next, the mitochondrial membrane potential of cells dissipated after the cells were treated by resveratrol. Moreover, we found that pro‐caspase 9 was downregulated and cytochrome c released from mitochondrial to the cytosol. We also found that the expression ratio of Bax/Bcl‐2 was increased in the treated cells. We finally showed that resveratrol inhibited the proliferation of SGC‐7901 xerograph in vivo . Conclusions Collectively, our findings demonstrate that resveratrol triggers apoptosis via mitochondrial pathway in SGC‐7901 cells, which provide more basis for resveratrol acting as antitumor agents in cancer therapy.
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Abstract Resveratrol, a polyphenol found in fruits, has been demonstrated to activate Sir2. Though many studies have demonstrated that resveratrol can activate SIRT1, whether it has effect on other sirtuins (SIRT2–7) are unknown. The present study shows that exposure of H9c2 cells to 50 µM H 2 O 2 for 6 h caused a significant increase in apoptosis, as evaluated by TUNEL and flow cytometry (FCM), but pretreatment of resveratrol (20 µM) eliminated H 2 O 2 ‐induced apoptosis. Resveratrol also prevented H 2 O 2 ‐induced caspase‐3 activation. Exposure of cells to resveratrol caused rapid activation of SIRT1,3,4,7. Sirtuin inhibitor, nicotinamide (20 mM) attenuated resveratrol's inhibitory effect on cell apoptosis and caspase‐3 activity. These results suggest that resveratrol protects cardiomyocytes from H 2 O 2 ‐induced apoptosis by activating SIRT1,3,4,7. J. Cell. Biochem. 107: 741–747, 2009. © 2009 Wiley‐Liss, Inc.
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Background and objectives
Resveratrol is a naturally occuring polyphenol produced in many plants (red grapes, raspberries, blueberries, etc.). The positive health effects of resveratrol are due its potent anti-inflammatory, anti-oxidant and anti-proliferative activities in many types of cancer cells. Due to the fact that resveratrol is sensitive to oxygen and is almost insoluble in water, its therapeutic application is very limited. Therefore, work is going on designing resveratrol analogues to improve the solubility and bioavailability of the natural resveratrol. Recently, we designed and synthesised a resveratrol prodrug (FEHH4–1) which is only active within the cells. Through esterification of all three phenolic groups, stability as well as lipophilicity of the natural resveratrol could be improved. In the present study, we compared the effects of resveratrol with FEHH4–1 on Jurkat T- cells.Material and methods
Jurkat T- cells were stimulated with PMA/PHA in the absence or presence of different concentrations of resveratrol or FEHH4–1. Modulation in IL-2 promoter activity was monitored by a IL-2 luciferase reporter assay. IL-2 release was quantified by enzyme-linked immunosorbent assay (ELISA). The effects of resveratrol and FEHH4–1 on cell proliferation and apoptosis were evaluated by XTT assay, Annexin-V/7-AAD staining and Western blot.Results
Both resveratrol and FEHH4–1 effectively attenuated IL-2 promoter activity and IL-2 expression in stimulated Jurkat T- cells. At a concentration of 25 µM, resveratrol blocked IL-2 production at about 50%, FEHH4–1, however, at about 80%. Additionally, we observed that FEHH4–1 reduced cell proliferation and induced apoptotic cell death at significantly lower concentrations than resveratrol.Conclusion
The resveratrol prodrug FEHH4–1 significantly amplified the beneficial effects of resveratrol in Jurkat T- cells. In comparison to resveratrol, FEHH4–1 enhanced downregulation of IL-2 production, and decreased proliferation rate in Jurkat T- cells. These data indicate that FEHH4–1 could be a substitute for the natural resveratrol in the future.Jurkat cells
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