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ABSTRACT: Selenium and zinc are well-known essential trace elements with potent biological functions. However, the possible health benefits of the combined administration of dietary selenium and zinc have not been studied extensively. In this study, we prepared selenium- and zinc-enriched mushrooms (SZMs) containing increased levels of selenium and zinc. The effects of SZMs on antioxidant and antitumor activities were evaluated. Mice were fed with either a control diet or a diet supplemented with SZMs or sodium selenite and zinc sulfate for 6 weeks. Antioxidant capacity was investigated by measuring the activities of antioxidant enzymes and the levels of lipid peroxide products. Results showed that treatment with SZMs significantly increased the activities of glutathione peroxidase (GPx) and superoxide dismutase and decreased the levels of malondialdehyde and lipofuscin. Furthermore, using a mouse model of lung tumors, we found that SZMs significantly decreased the number of tumor nodes with an increase in the activity of GPx. SZMs had a greater effect on the increase in both antioxidant and antitumor activities than did sodium selenite and zinc sulfate. These findings suggest that SZMs may be effective for improving antioxidant capacity and preventing tumors.
Biological trace element research 05/2012; · 1.92 Impact Factor
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ABSTRACT: We investigate the cytoprotective effects and the molecular mechanism of genistein in oxidative stress-induced injury using an endothelial cell line (EA.hy926). An oxidative stress model was established by incubating endothelial cells with H2O2. According to the present results, genistein pretreatment protected endothelial cells against H2O2-induced decreases in cell viability and increases in apoptosis. Genistein also prevented the inhibition of B-cell lymphoma 2 and the activation of caspase-3 induced by H2O2. Genistein increased superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels and attenuated the decrease in these antioxidants during oxidative stress. We also found that genistein induced the promoter activity of both nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ. Additionally, genistein induced the nuclear translocation of Nrf2 and PPARγ. While genistein caused the up-regulation of both Nrf2 and PPARγ, it also activated and up-regulated the protein expression and transcription of a downstream protein, haem oxygenase-1 (HO-1). Moreover, the use of Nrf2 small interfering RNA transfection and HO-1- or PPARγ-specific antagonists (Znpp and GW9662, respectively) blocked the protective effects of genistein on endothelial cell viability during oxidative stress. Therefore, we conclude that oxidative stress-induced endothelial cell injury can be attenuated by treatment with genistein, which functions via the regulation of the Nrf2 and PPARγ signalling pathway. Additionally, the endogenous antioxidants SOD, CAT and GSH appear to play a role in the antioxidant activity of genistein. The present findings suggest that the beneficial effects of genistein involving the activation of cytoprotective antioxidant genes may represent a novel strategy in the prevention and treatment of cardiovascular endothelial damage.
The British journal of nutrition 05/2012; · 3.45 Impact Factor
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ABSTRACT: Vascular endothelial dysfunction induced by oxidative stress has been demonstrated to be the initiation step of atherosclerosis (AS), and flavonoids may play an important role in AS prevention and therapy. Twenty-three flavonoids categorized into flavones, flavonols, isoflavones, and flavanones, all with 4-oxo-pyronenucleus, were examined for what structural characteristics are required for the inhibitory effects on endothelial dysfunction induced by oxidized low-density lipoprotein (oxLDL). Human vascular endothelial cells EA.hy926 were pretreated with different 4-oxo-flavonoids for 2 hs, and then exposed to oxLDL for another 24 hs. Cell viability and the level of malondialdehyde (MDA), nitric oxide (NO) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured, respectively. Then, correlation analysis and paired comparison were used to analyze the structure-activity relationships. Significant correlations were observed between the number of -OH moieties in total or in B-ring and the inhibitory effectson endothelial dysfunction. Furthermore, 3',4'-ortho-dihydroxyl on B-ring, 3-hydroxyl on C-ring and 2,3-double bondwere correlated closely to the inhibitory effects of flavonolson cell viability decrease and lipid peroxidation. 5,7-meta-dihydroxyl group on A-ring was crucial for the anti-inflammatory effects of flavones and isoflavones in endothelial cells. Moreover, the substituted position of B-ring on C3 rather than C2 was important for NO release. Additionally, hydroxylation at C6 position significantly attenuated the inhibitory effects of 4-oxo-flavonoids on endothelial dysfunction. Our findings indicated that the effective agents in inhibiting endothelial dysfunction include myricetin, quercetin, luteolin, apigenin, genistein and daidzein. Our work might provide some evidence for AS prevention and a strategy for the design of novel AS preventive agents.
International Journal of Molecular Sciences 01/2011; 12(9):5471-5489. · 2.60 Impact Factor
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ABSTRACT: We have previously selected a promising anti-cancer agent 3,6-dihydroxyflavone by pharmacodynamic experiments. In the present study, we investigated its pro-apoptosis mechanisms in leukemia HL-60 cell. Our data revealed that 3,6-dihydroxyflavone dose- and time-dependently decreases cell viability and induces apoptosis by activating caspase cascade, cleaving poly (ADP-ribose) polymerase (PARP). The anti-cancer effects of 3,6-dihydroxyflavone are associated with the generation of reactive oxygen species, the altered glutathione-redox balance as significantly decreased glutathione (GSH) and its ratio to gluthatione disulfide (GSSG), and the accumulation of lipid peroxidation indicator malondialdehyde. Addition of antioxidant N-acetylcysteine (NAC) prevents the elevation of reactive oxygen species induced by 3,6-dihydroxyflavone and partially suppresses the cytotoxic effects. Furthermore, 3,6-dihydroxyflavone reduces cell membrane fluidity and induces the loss of mitochondrial membrane potential. 3,6-Dihydroxyflavone was also found to modulate the activities of mitogen-activated protein kinase (MAPK) family members, which includes increased protein kinase of 38 kDa (p38), c-Jun N-terminal kinase (JNK), and decreased extracellular signal-regulated kinase (ERK) activation. The effect of 3,6-dihydroxyflavone on MAPKs pathway could be abrogated by co-treatment with NAC. Taking together, our data suggested that 3,6-dihydroxyflavone increases intracellular oxidative stress and lipid peroxidation, thereby affecting the physical and functional properties of plasma membrane, as well as MAPKs signal pathway, which are likely to play a role in the 3,6-dihydroxyflavone-induced HL-60 cell cytotoxicities.
European journal of pharmacology 12/2010; 648(1-3):31-8. · 2.59 Impact Factor
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HUI CHANG,
MANTIAN MI,
WENHUA LING,
JUNDONG ZHU,
QIANYONG ZHANG,
NA WEI,
YONG ZHOU,
YONG TANG,
XIAOPING YU,
TIN ZHANG,
JIAN WANG,
JIALIN YUAN
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ABSTRACT: The cytotoxicity and apoptosis induction effect of 23 flavonoids on human leukemia cells (HL-60) were investigated. 3,6-Dihydroxyflavone, luteolin and geraldol showed the most potent cytotoxic effect. By comparing the cytotoxicity of selected molecules that differ in only one structure element, we identified several structural properties important for potent cytotoxic activity, including the presence of 2,3-double bond, appropriate hydroxyl numbers, 3-OH and ortho-OH in ring B. Flavonoids with a 5-OH exhibited lower cytotoxicity than their counterparts. The intracellular reactive oxygen species (ROS) detection showed that 3,6-dihydroxyflavone, luteolin and geraldol all caused ROS generation. Addition of antioxidant N-acetylcysteine prevented the elevation of ROS induced by the three flavonoids and partially suppressed their cytotoxic effects. It implied that pro-oxidation was involved in the apoptotic response, and ROS generation plays an important role in the antitumor effect of flavonoids.PRACTICAL APPLICATIONSFlavonoids exist extensively in foods and herbal products, and several beneficial biological activities have been demonstrated. Development of compounds with anticancer and other pharmacological effects from natural products has currently become a very important topic. Our study revealed structurally related anticancer activities of 23 flavonoids on HL-60 cells and indicated that 3,6-dihydroxyflavone, luteolin and geraldol were active anticancer compounds via pro-oxidation and apoptosis induction. These findings should be useful for developing potent anticancer compounds from flavonoids for potential clinical application.
Journal of Food Biochemistry 03/2010; 34(s1):1 - 14. · 0.81 Impact Factor
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Fang Chen,
Mantian Mi,
Qianyong Zhang,
Na Wei,
Ka Chen,
Hongxia Xu,
Jialin Yuan,
Yong Zhou,
Haibin Lang,
Xiaoping Yu,
Bin Wang,
Jian Wang,
Yong Tang, Hui Chang
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ABSTRACT: We investigated whether taurine indirectly protects neurons under hypoxia by affecting retinal Müller cells, which are known to play important roles in the regulation of retinal glutamate content.
Retinal cells isolated from rats were exposed to hypoxia for 24 h. We evaluated the retinal neuron survival, glutamate content in cultures with and without taurine under hypoxic conditions. The glutamate clearance function correlated with the expression of glutamine synthetase (GS) mRNA and L-glutamate/L-aspartate transporter (GLAST) mRNA. Immunohistochemical staining of glial fibrillary acidic protein (GFAP), vimentin and S-100 protein was performed to examine cytoskeletal changes in retinal Müller cells.
Retinal neurons treated with taurine exhibited significantly higher survival rates than those without taurine under hypoxia. Taurine inhibited the upregulation of GFAP and vimentin, and inhibited the downregulation of GLAST, GS and the nuclear-cytoplasmic ratio of S-100 under hypoxia. In addition, taurine inhibited the upregulation of the glutamate content in neurons and retinal Müller cells upon hypoxic exposure.
These data suggest that hypoxic damage to cultured retinal cells is decreased by taurine. The neuroprotection by taurine may relate to buffering glutamate homeostasis via modulation of the glutamate clearance by retinal Müller cells.
Ophthalmic Research 01/2010; 44(2):105-12. · 1.56 Impact Factor
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ABSTRACT: Anthocyanins may play an important role in atherosclerosis prevention. However, the structure-function relationships are not well understood. The objective of this study was to compare the inhibitory effect of 21 anthocyanins against oxidized low-density lipoprotein-induced endothelial injury to understand the relationship between anthocyanin chemical structure and the endothelial protective properties, measured as cell viability, MDA production and NO release. Additionally, the intracellular anti-radical activity of the selected anthocyanins was investigated to identify the correlation with endothelial protection. Our results provide evidence that the number of -OH in total or in B-ring, 3',4'-ortho-dihydroxyl and 3-hydroxyl are the main structural requirements of anthocyanins in suppressing oxidative stress-induced endothelial injury and such inhibitory effect was significantly correlated with the intracellular radical scavenging activity.
FEBS letters 12/2009; 584(3):583-90. · 3.54 Impact Factor
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Xiaoping Yu,
Yuanqiong Luo,
Yong Zhou,
Qianyong Zhang,
Jian Wang,
Na Wei,
Mantian Mi,
Jundong Zhu,
Bin Wang, Hui Chang,
Yong Tang
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ABSTRACT: It is well established that statins display potent anticancer activity in several types of proliferating tumor cells. However, how to promote the sensitivity of statins to mammary cancer is yet to be completely deciphered. The purpose of this study was to investigate whether breast cancer susceptibility gene 1 (BRCA1) overexpression sensitizes mammary cancer cells to statins. MCF-7 cells, which have only one wild-type BRCA1 allele, were transfected with pcDNA3-beta-HA-hsBRCA1 plasmids via liposomes to reconstitute BRCA1 overexpression human breast cancer cell line, and tumoral xenografts with BRCA1 overexpression were subsequently established in BALB/c nude mice. Then, the inhibitory activity of lovastatin on cancer cells and tumoral xenografts, and the underlying mechanism involving in cell-cycle regulatory proteins were analyzed. The proliferative ability of MCF-7 cells treated with lovastatin was reduced compared to normal, and further decreased in the presence of excess BRCA1, detected by methyl thiazolyl tetrazolium and flow cytometry techniques in vitro or by 5-bromodeoxyuridine incorporation in vivo. Additionally, the mRNA and protein expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and retinoblastoma protein (pRb), was further down-regulated under exposure to lovastatin in condition of BRCA1 overexpression, but the expression of p21WAF1/CIP1, a cyclin-dependent kinase inhibitor (CDKI), was further up-regulated, both in vitro and in vivo detected with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Moreover, we found the further reduced volume of tumoral xenografts treated with lovastatin in the presence of BRCA1 overexpression. Our results suggest that BRCA1 overexpression sensitizes cancer cells to lovastatin via regulation of cyclin D1-CDK4-p21WAF1/CIP1 pathway, which will provide an innovative experimental framework to study control of breast cancer cell proliferation.
International Journal of Oncology 10/2008; 33(3):555-63. · 2.40 Impact Factor
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ABSTRACT: Flavonoids exist extensively in the human diet, and a variety of health effects have been ascribed to them. The cytotoxic effects of 23 flavonoids on breast cancer cells (MDA-MB-231 and MCF-7), colorectal carcinoma cells (LoVo and DLD-1) and prostatic cancer cells (PC3) were investigated. By comparing the cytotoxicity (EC(50)) of selected molecules that differ in only one structure element, we identified several structural properties associated with enhanced cytotoxicity, including the presence of the 2,3-double bond, appropriate hydroxyl numbers, 3-OH, 6-OH and ortho-hydroxylation in ring B. Flavonoids with a 5-OH exhibited lower cytotoxicity than their non-hydroxylated counterparts. Results indicated that 3,6-dihydroxylflavone showed the most potent cytotoxic effect on these cancer cells. The appearance of apoptotic cells with DAPI staining was observed in cancer cells under 3,6-dihydroxylflavone treatment, and the apoptosis analysis by flow cytometry also showed that 3,6-dihydroxylflavone induced apoptotic cell death in these cancer cells. These results revealed the structurally related toxicity of flavonoids on human cancer cells, and indicates that 3,6-dihydroxylflavone is an active compound worthy of development for cancer chemotherapy.
Archives of Pharmacal Research 10/2008; 31(9):1137-44. · 1.59 Impact Factor
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ABSTRACT: In this study, the effects of dietary fatty acids on the fatty acid compositions and lipid metabolic-related genes expression in N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinogenesis were evaluated. The 50-day-old female Sprague-Dawley rats were intervened by different dietary fats (15% wt/wt), including saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-6 polyunsaturated fatty acid (PUFA), n-3 PUFA, 1:1 n-6/n-3, 5:1 n-6/n-3, 10:1 n-6/n-3, and 1:2:1 S/M/P (1:1 n-6/n-3), alone or in combination with MNU. There was no mammary tumor occurrence in the control and MNU-treated n-3 PUFA groups after 18 wk. n-3 PUFA diet retarded the weight growth of rats. 1:1 n-6/n-3 diet significantly reduced the MNU-induced tumor incidence and tumor multiplicity compared with SFA, MUFA, n-6 PUFA, 5:1 n-6/n-3, 10:1 n-6/n-3 and 1:2:1 S/M/P diets (42.86% vs. 83.33%-92.31%, 0.79 vs. 2.62-2.85, P < 0.01). Additionally, 1:1 n-6/n-3 diet substantially increased cis-5,8,11,14,17-eicosapentaenoic acid and cis-4,7,10,13,16,19-docosahexaenoic acid levels, whereas it decreased C20:4 level and the mRNA expressions of fatty acid synthase, Cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) in mammary tissues (P < 0.05). These results suggest that 1:1 n-6/n-3 in the diet is effective in the prevention of mammary tumor development by increasing the n-3 PUFA content and reducing the expression of lipid metabolic-related genes.
Nutrition and Cancer 02/2008; 60(6):810-25. · 2.78 Impact Factor
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ABSTRACT: Flavonoids, with some beneficial biological activities, exist extensively in foods and herbal products. This study was to evaluate the effects of 23 flavonoids on the proliferation of leukemia cell line HL-60, and elucidate the structure-activity relationship (SAR).
HL-60 cells were treated with 23 flavonoids with high purity and definite structure. Cell proliferation was detected by MTT assay. The 50% inhibition concentrations (IC50) of the 23 flavonoids were calculated. The effects of particular structures on IC50 were evaluated.
Most of the 23 flavonoids inhibited the proliferation of HL-60 cells distinctly, and the effects were enhanced along with increasing concentrations. However, the intensity of their effects were different, which were arranged from strong to weak as follows:3,6-dihydroxyflavone > luteolin > geraldol > 2'-hydroxyflavanone > apigenin > 3,7-dihydroxyflavone > myricetin > fisetin > baicalein > quercetin > flavanone > chrysin > galangin > 4'-hydroxyflavanone > 6-hydroxyflavone > genistein > flavone >7-hydroxyflavone > daidzein > hesperetin > naringenin. The 2,3-double bond in ring C, appropriate hydroxyls, ring B attached at position 2, hydroxyls in position 3, ortho-substituting hydroxyls in ring B were related to enhanced inhibitory effects of flavonoids on the proliferation of HL-60 cells, while the lack of 2,3-double bond, deficiency or redundancy of hydroxyl groups, hydroxyl group in position 5, 7 or meta-substituting hydroxyls in ring B, isoflavone structure were related to reduced inhibitory effects of flavonoids.
The 2,3-double bond in ring C, appropriate hydroxyls, ring B attached at position 2, hydroxyls in position 3, ortho-substituting hydroxyls in ring B may be key structural requirements of flavonoids for potent cytotoxicity to HL-60 cells.
Ai zheng = Aizheng = Chinese journal of cancer 01/2008; 26(12):1309-14.
