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1.
Sun CY  Hu Y  Guo T  Wang HF  Zhang XP  He WJ  Tan H 《Acta pharmacologica Sinica》2006,27(11):1447-1452
AIM: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. METHODS: The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-x(L), XIAP and Bax protein were detected using Western blotting analysis. RESULTS: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-x(L) and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64+/-8 micromol/L, 93+/-11 micromol/L, and 153+/-11 micromol/L, respectively.Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity. CONCLUSION: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.  相似文献   

2.
Objective The increasing recognition of the role for oxidative stress in hepatic disorders has led to extensive investigation on the protection by exogenous antioxidants against hepatic injury.In this study,we choose two typical polyphenol,quercetin and rutin,to investigate the mechanism of induction of cellular antioxidants and phase 2 enzymes in human HepG2 cells.Methods The HepG2 cells were treated with various concentrations of quercetin and rutin for 6 h and 24 h.The activities of NAD(P)H:quinone oxidoreductase(NQO1)in HepG2 cells were measured by 2,6-dichloroindophenol reduction method.The content of superoxide dismutase(SOD)was determined with the method of chemical colorimetry.The protein expressions of NQO1 and NF-E2-related factor 2(Nrf2)in HepG2 cells were detected by Western blotting.Results Incubation of HepG2 cells with quercetin and rutin resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes,including NQO1,SOD.Quercetin and rutin treatment of HepG2 cells also caused increase in protein expressions of NQO1 and Nrf2.Conclusions This study demonstrates that a series of phase 2 enzymes in HepG2 cells can be induced by quercetin and rutin in a concentration-and time-dependent fashion by upregulation the protein expression of nrf2.  相似文献   

3.
Resveratrol (3,4',5-trihydroxystilbene), a polyphenolic compound found in mulberries, grapes and red wine has been demonstrated to be capable of protecting against oxidative cardiovascular pathophysiology. However, the underlying cellular and biochemical mechanisms remain to be elucidated. This study was undertaken to determine if resveratrol could upregulate endogenous antioxidants and phase 2 enzymes in cultured aortic smooth muscle cells (ASMCs), and if such increased cellular defenses could provide protection against oxidative and electrophilic vascular cell injury. Incubation of rat ASMCs with resveratrol at low micromolar concentrations resulted in a significant induction of a scope of cellular antioxidants and phase 2 enzymes in a concentration- and/or time-dependent fashion. These cytoprotective factors include superoxide dismutase, catalase, glutathione, glutathione reductase, glutathione peroxidase, glutathione S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NOQ1). Notably, induction of catalase, GST, and NOQ1 was most remarkable among the above resveratrol-inducible antioxidants and phase 2 enzymes. Moreover, resveratrol treatment also significantly increased the mRNA expression of catalase, GSTA1, and NQO1 in a time-dependent manner. Pretreatment of ASMCs with resveratrol afforded a remarkable protection against xanthine oxidase (XO)/xanthine- or 4-hydroxy-2-nonenal-induced cytotoxicity, as assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Resveratrol pretreatment also led to a marked reduction in intracellular accumulation of reactive oxygen species in ASMCs after incubation with XO/xanthine. Taken together, this study demonstrates that a scope of key endogenous antioxidants and phase 2 enzymes in cultured ASMCs can be upregulated by resveratrol at low micromolar concentrations, and that such chemically-elevated cellular defenses rendered cells increased resistance to oxidative and electrophilic stress. The results of this study thus suggested a new mechanism, which might contribute to the cardiovascular protective effects of resveratrol.  相似文献   

4.
Vascular smooth muscle cell (VSMC) proliferation is pivotal in the progression of hypertension, atherosclerosis, and restenosis. Resveratrol is a grape polyphenol that is implicated as an important contributor to red wine's vascular protective effects. Its antimitogenic action on VSMC is attributed to an array of pleiotropic effects, including modulation of the estrogen receptor (ER). To elucidate the mechanisms underlying resveratrol-mediated ER modulation and its inhibition of VSMC proliferation, we treated VSMC with resveratrol with or without the ER antagonist ICI 182,780 and measured cell proliferation and nitric oxide (NO) production. Resveratrol dose-dependently decreased VSMC DNA synthesis, with a half maximal inhibitory concentration (IC50) of 3.73+/-0.57 microM, and dramatically slowed cell growth, but did not induce VSMC apoptosis. Resveratrol-mediated decrease in proliferation was reversed by cotreatment with ICI 182,780, and resveratrol effectively competed with 17beta-estradiol for binding to the ER, exhibiting an IC50 of 8.92+/-0.14 microM. Resveratrol induced a sustained increase in ER-dependent NO production. Further, resveratrol-mediated decrease in VSMC proliferation was blunted by cotreatment with the general nitric oxide synthase (NOS) inhibitor N5-(1-Iminomethyl)-L-ornithine, dihydrochloride or with the inducible NOS (iNOS)-selective inhibitor S,S'-1,4-phenylene-bis (1,2-ethanediyl)bis-isothiourea, dihydrobromide, but not with the neuronal NOS-selective inhibitor 7-nitroindazole. Though resveratrol did not alter iNOS protein levels, it dose-dependently increased levels of iNOS activity, of the iNOS cofactor tetrahydrobiopterin (BH4), and of guanosine triphosphate cyclohydrolase I protein, the rate-limiting enzyme in BH4 biosynthesis. In addition, all of these effects were abolished by cotreatment with ICI 182,780. Thus, the antimitogenic effects of resveratrol on VSMC may be mediated by an ER-induced increase in iNOS activity.  相似文献   

5.
白藜芦醇抑制HepG2细胞生长及诱导细胞凋亡的初步研究   总被引:8,自引:1,他引:7  
目的 研究白藜芦醇 (Res)对人肝癌HepG2细胞生长增殖的影响 ,进而探讨Res诱导HepG2细胞凋亡的作用。方法 用不同浓度的Res处理HepG2细胞 ,MTT法检测Res对HepG2细胞生长增殖的抑制作用 ,通过HE染色、透射电子显微镜、原位末端标记法 (TUNEL)和流式细胞术观察凋亡细胞的形态结构变化以及定性、定量检测细胞凋亡。结果 Res能抑制HepG2细胞的生长增殖 ,并呈浓度依赖性 ;Res能诱导HepG2细胞凋亡。 结论 Res能够通过诱导HepG2细胞凋亡抑制HepG2细胞的增殖。  相似文献   

6.
Vascular smooth muscle cells (VSMCs) play an important role in normal vessel formation and in the development and progression of cardiovascular diseases. Grape plants contain resveratrol monomer and oligomers and drinking of wine made from grape has been linked to “French Paradox”. In this study we evaluated the effect of vitisin B, a resveratrol tetramer, on VSMC behaviors. Vitisin B inhibited basal and PDGF-induced VSMC migration. Strikingly, it did not inhibit VSMC proliferation but inversely enhanced cell cycle progression and proliferation. Among the tested resveratrol oligomers, vitisin B showed an excellent inhibitory activity and selectivity on PDGF signaling. The anti-migratory effect by vitisin B was due to direct inhibition on PDGF signaling but was independent of interference with PDGF binding to VSMCs. Moreover, the enhanced VSMC adhesiveness to matrix contributed to the anti-migratory effect by vitisin B. Fluorescence microscopy revealed an enhanced reorganization of actin cytoskeleton and redistribution of activated focal adhesion proteins from cytosol to the peripheral edge of the cell membrane. This was confirmed by the observation that enhanced adhesiveness was repressed by the Src inhibitor. Finally, among the effects elicited by vitisin B, only the inhibitory effect toward basal migration was partially through estrogen receptor activation. We have demonstrated here that a resveratrol tetramer exhibited dual but opposite actions on VSMCs, one is to inhibit VSMC migration and the other is to promote VSMC proliferation. The anti-migratory effect was through a potent inhibition on PDGF signaling and novel enhancement on cell adhesion.  相似文献   

7.
目的:动态观察氟哌啶醇季铵盐衍生物(F_3)对血管平滑肌细胞内钙浓度的影响。方法:利用激光共聚焦显微镜动态观察F_3(0.o1-10μmol/L)对由KCl(30mmol/L)诱导的大鼠血管平滑肌细胞钙荧光强度增加的作用。结果:KCl可诱发细胞内钙荧光强度迅速增强,F_3可以拮抗由KCl诱导的细胞内钙荧光强度增强作用,并呈量效依赖性和时间依赖性,终强度(KCl:67±24;F_3 0.o1μmol/L:57±13;0.1μmol/L:40±13;1μmol/L:29±9;10μmol/L:20±6)。在加入F_3后,钙荧光强度的变化最快时程是在给F_3后0-30s。结论:F_3拮抗血管收缩主要是由于阻断了Ca~(2 )通道。  相似文献   

8.
AIM: To investigate the effect of astilbic acid (3β, 6β-dihydroxyolean-12-en-27-oic acid, AA) on human colorectal carcinoma COLO 205 cell proliferation and apoptosis. METHODS: Proliferation of COLO 205 cells was measued by MTT assay. Content of DNA in COLO 205 cell was measued by modified diphenylamine assay. AA-induced morphological changes was observed with fluorescence microscope and transmission electron microscope. DNA fragmentation was visualized by agarose gel electrophoresis. Apoptosis rate and cell cycle distribution were determined by flow cytometric analysis. Expressions of Bcl-2 and Bax proteins were visioned by immunohistochemical analysis. The change of relative mitochondral transmembrane potential (MTP) in COLO 205 cell was analyzed with FCM after rhodamine 123 staining. RESULTS: The IC50 (96 h) of AA for inhibiting COLO 205 cell proliferation was 61.56 0.34 μmol/L. AA induced a marked concentration- and time-dependent inhibition of COLO 205 cell proliferation and reduced the DNA content in COLO 205 cell. Cells treated with AA 64 μmol/L showed typical morphological changes of apoptosis and DNA “ladder“ pattern. The cell cycle was arrested in G0/G1 phase, and the apoptosis rate was 28.25 % for COLO 205 cells treated with AA 64 μmol/L for 48 h. Meanwhile the expression of Bcl-2 protein was decreased while that of Bax was increased and relative MTP was decreased as well. DEVD-CHO1 μmol/L could increase the viability of COLO 205 cells treated with AA for 48 h. CONCLUSION: AA showed potent inhibitory activity on COLO 205 cells proliferation, and could induce COLO 205 cells apoptosis through disturbing DNA replication, down-regulating Bcl-2 expression, and up-regulating Bax expression, lowering relative MTP, and activating caspase-3 pathway.  相似文献   

9.
1. Oestrogen reduces vascular smooth muscle cell proliferation in mouse vascular injury models. Data on the antiproliferative effect of oestrogen in cultured vascular smooth muscle cells (VSMC) are less conclusive than those obtained in whole animal studies. 2. In the present study, we investigated the hypothesis that oestrogen-induced attenuation of VSMC proliferation is facilitated by the presence of endothelial cells (EC) using a coculture system of EC and VSMC. 3. Treatment with a physiological concentration of oestrogen (17beta-estradiol (E2); 100 nmol/L) had no effect on fetal calf serum (FCS)-stimulated DNA synthesis in either A7r5 VSMC or bEnd.3 EC. However, stimulation of bEnd. 3 cells with E2 in a coculture system of bEnd.3 and A7r5 cells reduced FCS-induced DNA synthesis in A7r5 cells by approximately 45%. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (l-NAME; 100 micromol/L) did not reverse the oestrogen-induced attenuation of DNA synthesis. The antiproliferative effect of E2 may be mediated via either oestrogen receptor (ER) alpha, ERbeta or both because the bEnd.3 cells expressed immunoreactivity for both ER subtypes. 4. These data show that ERalpha- and ERbeta-expressing endothelial cells, which are stimulated with a physiological concentration of oestrogen, release a factor(s) that arrests the proliferation of cocultured VSMC. Oestrogen-induced attenuation of vascular smooth muscle cell proliferation is not prevented by L-NAME, suggesting that a mechanism other than endothelial NO is involved.  相似文献   

10.
1. It has been well established that oestrogens can increase the number of endothelial progenitor cells (EPC) by anti-apoptotic effects. Resveratrol, a polyphenolic phytoalexin extracted from grapes and wine, has been reported to act as an oestrogen receptor agonist. We hypothesize that putative phyto-oestrogen may promote EPC proliferation and survival in vitro. 2. Endothelial progenitor cells were isolated from human peripheral blood and identified immunocytochemically. Endothelial progenitor cells were incubated with resveratrol (1, 10, 25 and 50 mmol/L) or control for specified times. Cell proliferation, migration and in vitro vasculogenesis were assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) assay, modified Boyden chamber assay and in vitro vasculogenesis detection, respectively. 3. Resveratrol increased the number of EPC and promoted EPC proliferation, adhesion and migration in a dose- and time-dependent manner. Cell number peaked at 50 mmol/L resveratrol after incubation for 24 h compared with vehicle control (61.3 +/- 5.8 vs 112.8 +/- 7.2, respectively; P < 0.01). 4. Furthermore, cell cycle analysis showed that 50 mmol/L resveratrol significantly increased the S phase and decreased the G(0)/G(1) phase of EPC. In addition, resveratrol increased vascular endothelial growth factor production and further induced vasculogenesis in vitro. 5. In conclusion, resveratrol significantly induces EPC proliferation, migration and further promotes angiogenesis in vitro.  相似文献   

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