Breast cancer is one of the leading causes of cancer-related deaths in women worldwide.It is a cancer that originates from the mammary ducts and involves mutations in multiple genes.Recently,the treatment of breast ca...Breast cancer is one of the leading causes of cancer-related deaths in women worldwide.It is a cancer that originates from the mammary ducts and involves mutations in multiple genes.Recently,the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness,which gives rise to therapeutic resistance.Epidemiological,populationbased,and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer.Diallyl disulfide(DADS)and diallyl trisulfide(DATS)are the main allyl sulfur compounds present in garlic,and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation,tumor metastasis,and angiogenesis.The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer.This review discusses the potential anticancer activities of DADS and DATS,with emphasis on drug resistance in triple-negative breast cancer(TNBC).Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC,especially in clinical studies.展开更多
AIM:To investigate the effects of diallyl trisulfide(DATS),a garlic-derived organosulfur compound,in pancreatic cancer cells.METHODS:Human pancreatic cancer cells with wildtype p53 gene(Capan-2)and normal pancreatic e...AIM:To investigate the effects of diallyl trisulfide(DATS),a garlic-derived organosulfur compound,in pancreatic cancer cells.METHODS:Human pancreatic cancer cells with wildtype p53 gene(Capan-2)and normal pancreatic epithelial cells(H6C7)were cultured in RPMI1640.DATS was prepared at a concentration of 100μmol/L.Cell viability was determined via the methyl thiazolyl tetrazolium assay.Apoptotic cells were detected by TUNEL assay.Cell cycle analysis was performed using flow cytometry.Protein expression was determined by Western blot.Bax and Bcl-2 expression was detected by immunofluorescence.Apoptosis genes and cell cycle were assessed by quantitative real-time polymerase chain reaction.RESULTS:DATS suppressed the viability of cultured human pancreatic cancer cells(Capan-2)by increasing the proportion of cells in the G2/M phase and induced apoptotic cell death.Western blot analysis indicated that DATS enhanced the expression of Fas,p21,p53and cyclin B1,but downregulated the expression of Akt,cyclin D1,MDM2 and Bcl-2.DATS induced cell cycle inhibition which was correlated with elevated levels of cyclin B1 and p21,and reduced levels of cyclin D1 in Capan-2 cells and H6C7 cells.DATS-induced apoptosis was markedly elevated in Capan-2 cells compared with H6C7 cells,and this was correlated with elevated levels of cyclin B1 and p53,and reduced levels of Bcl-2.DATS-induced apoptosis was correlated with downregulation of Bcl-2,Akt and cyclin D1 protein levels,and up-regulation of Bax,Fas,p53 and cyclin B protein levels in Capan-2 cells.CONCLUSION:DATS induces apoptosis of pancreatic cancer cells(Capan-2)and non-tumorigenic pancreatic ductal epithelial cells(H6C7).展开更多
Aim: To investigate the protective effect of diallyl sulfide (DAS), a constituent of garlic, against testosterone-induced oxidative stress in male Swiss albino mice. Methods: The animals were given low (250 mg/an...Aim: To investigate the protective effect of diallyl sulfide (DAS), a constituent of garlic, against testosterone-induced oxidative stress in male Swiss albino mice. Methods: The animals were given low (250 mg/animal) and high dose (500 mg/animal) of DAS in corn oil for 7 days along with testosterone (5 mg/kg body weight, i.p.). At the end of the study period, the prostate and the liver were dissected to determine various antioxidant enzyme levels (catalase, superoxide dismutase, glutathione reductase, glutathione-s-transferase) and lipid peroxidation. Results: In testosterone treated mice, depleted antioxidant enzyme level was accompanied with enhancement in lipid peroxidation in prostate and liver. DAS significantly restored the testosterone-induced antioxidant enzymes and lipid peroxidation in the both organs. These changes appear to be mediated by the antioxidant-enhancing effects of DAS. Conclusion: The results of the present study suggest that DAS is effective in exerting antioxidant effects by inhibiting testosterone-induced oxidative stress and might be helpful in preventing prostate cancer.展开更多
The inhibitory effects of diallyl sulfide(DAS) derived from allicin on in vitro and in vivo proliferation of human osteosarcoma MG-63 cells and the action mechanism,and the influence of DAS on invasive capability of M...The inhibitory effects of diallyl sulfide(DAS) derived from allicin on in vitro and in vivo proliferation of human osteosarcoma MG-63 cells and the action mechanism,and the influence of DAS on invasive capability of MG-63 cells were investigated in order to search for the novel medicines for osteosarcoma.In the in vitro experiment,MG-63 cells were treated with different concentrations of DSA,and the morphological changes of MG-63 cells were observed under an inverted phase microscope.MTT method was used to assay the proliferation of MG-63 cells.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) was used to detect the VEGF mRNA expression level in MG-63 cells.By using Transwell invasion assay,the influence of DAS on invasive ability of MG-63 cells was tested.In the in vivo experiment,the nude mice MG-63 cells tumor-bearing model was established,and different concentrations of DAS were injected beside the tumor.Twenty-one days after treatment,the mice were killed,the tumor size and tumor inhibition rate were calculated.The microvessel density(MVD) was determined by using immunohistochemistry.In the in vitro experiment,different concentrations of DAS could obviously inhibit proliferation of MG-63 cells in a time-and concentration-dependent manner.RT-PCR revealed that the expression levels of VEGF mRNA in DSA groups(different concentrations) were significant reduced as compared with those in control group(all P<0.05).Transwell invasion assay indicated that in 20 and 40 μg/mL DAS groups,the number of migratory cells was 91.4±8.3 and 81.8±7.4 respectively,which was significantly declined as compared with that in control group(150.4±14.7,both P<0.05).In the in vivo experiment,DAS could significantly suppress the growth of MG-63 tumor-bearing tissue.Immunohistochemistry demonstrated that different concentrations(20 and 40 μg/mL) of DAS could significantly decrease MVD of MG-63 tumor-bearing tissue(all P<0.05).It was suggested that DAS could inhibit the growth of MG-63 cells probably by suppressing the expression of VEGF mRNA.展开更多
It has been reported that diallyl sulfide (DAS), a sulfur-containing volatile compound in garlic (Allium sativum ), exerts anticarcinogenic activity in various rodent tumor models. In the present study, the antitumor ...It has been reported that diallyl sulfide (DAS), a sulfur-containing volatile compound in garlic (Allium sativum ), exerts anticarcinogenic activity in various rodent tumor models. In the present study, the antitumor property of DAS was tested in Swiss albino mice in the two steqe initiation-promotion mouse skin carcinogenesis. Skin cancers were initiated topically with a single subcarcinOgenic dose (52μg) of 7, 12-dimethyl benz (a) anthracene (DMBA). Promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5μg/animal for 32 weeks. DAS was applied topically (250μg/animal) thrice weekly for 3 weeks for anti-initiating and 1 h prior to each promotion treatment for anti-promoting studies. The results showed that the treatment schedule of DAS can effectively delay the onset of tumorigenesis and reduce the cumulative number of tumors and the average number of tumors per mouse. In groups in which DAS applied prior to initiation or promotion, a significant population of the aniinals remained tumor-free till the termination of experiment. These findings suggest that DAS can effectively inhibit chemically induced mouse skincarcinogenesis.展开更多
The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-o...The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-operated group (group S, n=8), sepsis model group (group C, n=24), diallyl trisulfide (DATS)-treated group (group D, n=24). Animals in groups C and D were further divided into three subgroups according to different observation time points, with 8 rats in each sub-group.Rats in group D and C were intravenously injected with normal saline or DATS respectively at a dose of 20 mg/kg after the establishment of sepsis model. Eight rats in groups C and D were sacrificed at 3, 6 and 24 h post-CLP and their livers were harvested for detection of interleukin (IL)-1 receptor associated kinase-4 (IRAK-4), nuclear factor-κB (NF-κB), c-fos, c-jun, malondialdehydethhe (MDA) and superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α) and for pathological examination. The results showed that the levels of serum IRAK-4, NF-κB and TNF-α in hepatic tissues were higher in group C than group S (control group) (P<0.05). After DATS treatment, the levels of IRAK-4 and NF-κB in the hepatic tissues and serum TNF-α in group D were lower than those in group C (P<0.05). The levels of c-fos and c-jun and MDA in the hepatic tissues were higher in group C than in group S (P<0.05). After DATS treatment, the levels of c-fos and c-jun and MDA in the hepatic tissues were significantly lower in group D than in group C (P<0.05). When compared with group S group, concentration of SOD in the hepatic tissues in group C was significantly lower (P<0.05). After DATS treatment, the concentration of SOD in the hepatic tissues was higher in group D than in group C (P<0.05). These findings suggested that treatment with DATS could ameliorate sepsis-induced liver injury in rats. The protective effect might be related to its ability to inhibit the signal pathway of IRAK-4 and NF-κB, thereby decreasing the production of oxygen free radicals and down-regulating the expression of c-fos and c-jun.展开更多
At high concentration (50 μg/ml), diallyl trisulfide (DATS) had an inhibitory effect on T cell activation (compared with control group, P<0.05). But at appropriate concentrations(3.125-12. 5 μg/ml). DATS augmente...At high concentration (50 μg/ml), diallyl trisulfide (DATS) had an inhibitory effect on T cell activation (compared with control group, P<0.05). But at appropriate concentrations(3.125-12. 5 μg/ml). DATS augmented the activation of T lymphocytes by Con A (compared with control group, P<0. 01). The augmentation of T cell activation by DATS was related to its inhibitory effect on the production of nitric oxide (NO) by macrophages.In a wide range of concentrations (1-100 μg/ml) , DATS can inhibit the production of NO by macrophas,es (P<0.05,P<0.01). In addition, DATS can antagonize the inhibition of tumor-derived immunosuppressive factors produced by S180 cells and Ehrlich ascitic cancer cells on the activation of T cells, and reduce the inhibitory rate significantly (P<0.01). DATS, despite its inhibition of the production of NO by macrophages, can significantly enhance the production of hydrogen peroxide (H2O2 by macrophages.When macrophages were pretreated with DATS for 24 h, the cytotoxicity % of macrophages to three tumor cell lines was significantly higher than that in corresponding control group (P<0.05,P<0.01). In the presence of both DATS and LPS, the cytotoxicity of macrophages was further enhanced so that the cytotoxicity % of macrophages to tumor cells was significantly higher than either that in the presence of DAIS alone or that in the presence of LPS alone(P<0.05, P<0.01). These results indicate that DATS can augment the activation of T cells and enhance the anti-tumor function of macrophage, suggesting that DATS may be potentially useful in tumor therapy.展开更多
Objective To explore the production and cytotoxicity of the reactive oxygen species(ROS)induced by diallyl trisulfid(DATS)in HL-60 cells.Methods HL-60 cells were either treated with various doses of DATS alone,or DATS...Objective To explore the production and cytotoxicity of the reactive oxygen species(ROS)induced by diallyl trisulfid(DATS)in HL-60 cells.Methods HL-60 cells were either treated with various doses of DATS alone,or DATS combination with Apocynin,a specific NADPH oxidase inhibitor,or with antioxidant N-acetyl-L-cysteine(NAC)for 0,1,3,6,12 and 24 hours,respectively.The intracellular ROS level was measured by flow cytometry.The activity of NADPH oxidase was evaluated by NBT reduction experiment.The content of both malondialdehyde(MDA)and the protein carbonyl was analyzed by spectrophotometer.Results The results from flow cytometry indicated that DATS significantly increased the intracellular ROS level in HL-60 cells(P<0.05),which is a dose-and time-dependent.The fluorescence intensities of ROS reached at maximuam when HL-60 cells were incubated with 150 μmol·L-1 DATS for 3 hours.The NBT reduction experiment showed that DATS activated NADPH oxidase which had highest activity when cell were exposed to 150 μmol·L-1 DATS for 3 hours.Results DATS induced MDA and protein carbonyl production in HL-60 cells.Furrthermore,both MDA and protein carbonyl in the cells exposed to 150 μmol·L-1 DATS for 3 hours reached the highest level.Apocynin and NAC could attenuate the production of MDA and protein carbonyl,which suggested that ROS induced by DATS was involved in the toxicity to cells.Conclusions DATS induce ROS production through activating NADPH oxidase in HL-60 cells.ROS induced by DATS increase the oxidation of the membrane lipid and the protein of HL-60 cell.展开更多
Objective To explore the effect and mechanism of diallyl trisulfide on the activity of NADPH oxidase in Hl-60 cells.Methods HL-60 cells were treated with DATS at a indicated concentration for 0,1,3,6,12 hours,respecti...Objective To explore the effect and mechanism of diallyl trisulfide on the activity of NADPH oxidase in Hl-60 cells.Methods HL-60 cells were treated with DATS at a indicated concentration for 0,1,3,6,12 hours,respectively.The activity of NADPH oxidase was measured by the reduction of the yellow dye nitroblue tetrazolium(NBT).The mRNA expression of NADPH oxidase subunits,including gp91phox,p47 phox,p22 phox,Rac2 and Rac1,was detected by RT-PCR.The protein expression of p67 phox,gp91 phox and Rac2 was analyzed by Western blot.The cell membrane fractions were prepared according to the instruction of Mem-PER kit from Pierce Corp.Results The results showed that reduction ability of HL-60 cells for NBT markedly increased in a concentration-dependent manner following DATS incubation for 3 and 6 hours(P<0.05).HL-60 cells treated by DATS at a concentration of 150 μM for 3 hours have a maximal reduction effect for NBT.The results from RT-PCR indicated that mRNA expression of NADPH oxidase subunits,including p47phox,gp91 phox,p22 phox,Rac2 and Rac1,significantly increased in a concentration-dependent manner in HL-60 cells treated by DATS.The results from western blot showed that HL-60 cells following DATS incubation have a higher level expression of Rac2 and gp91phox,compared with untreated-HL-60 cells.Our results also indicated that a maximal expression level of p47phox,gp91 phox,p22 phox,Rac2 and Rac1in HL-60 cells is present at 3 hours following DATS incubation.We found that levels of both Rac2 and p67phox was reduced in the cytosolic fraction and meanwhile increased in the membrane fraction following HL-60 exposed to DATS,Which is dependent on the concentration and time of DATS treatment.Furthermore,the level of both Rac2 and p67phox located to the plasma membrane translocation was maximized following 150 μM of DATS incubation for 3 hours.Conclusions DATS induce the activation of NADPH oxidase by both up-regulating the expression of NADPH oxidase subunit and translocating the cytosolic Rac2 and p67 phox subunit to the plasma membrane in HL-60 cells.展开更多
Mosl of anticancer drugs are mutagenic. A possible exeeption is diallyl .trisulfide(DAT ), a component of garlic. It is an antimutagenic anticunccr chemical although it ismainly uscd as antibiotic. Its modifying eff...Mosl of anticancer drugs are mutagenic. A possible exeeption is diallyl .trisulfide(DAT ), a component of garlic. It is an antimutagenic anticunccr chemical although it ismainly uscd as antibiotic. Its modifying effeci on induction of UDS by mutagenicmitomycin C (MMC), cyclophosphamide (CP) and cis-diamine dichloroplatin (DDP) was invcstigiltcd with the UDS assay in the primary cultures of Wistar rat hepatocytes (hpc)using the autoradiographic technique. Resultsshowed that 1.0-4.0 nmol/ml of DAT didnot inducc UDS and that MMC, CP and DDP resulted in a significant induction ofdosc-dependent UDS. DAT enhanced induction of UDS by these drugs. A dose-effectrclationship was observed betwecn dose of DAT and enhancement of induction of UDS.Howcvcr, thc mcchanism of the enhancement is not clear.展开更多
A new monomer, 3,9-diallyl-3, 9-dibenzyl-1, 5,7,11 - tetraoxa- spiro [5,5] undecane (6) was prepared by the reaction of 2- allyl- 2' - benzyl- propanediol - 1.3 with dibutyltin oxide, and then treated with CS_2. M...A new monomer, 3,9-diallyl-3, 9-dibenzyl-1, 5,7,11 - tetraoxa- spiro [5,5] undecane (6) was prepared by the reaction of 2- allyl- 2' - benzyl- propanediol - 1.3 with dibutyltin oxide, and then treated with CS_2. Monomer 4 could be initiated by cationic initiators to give a viscous polymer (white powder in the case of polymerization at 0℃). Upon the NMR and IR spectra of the obtained polymer, the components and their relative amount were estimated. The polymerization mechanism was discussed.展开更多
Diallyl Disulfide (DADS) is the main organosulfur component of garlic and it is known for multiple pharmacologicalactions. Currently, DADS has been well documented to ameliorate the testis injuries caused by X-rayirra...Diallyl Disulfide (DADS) is the main organosulfur component of garlic and it is known for multiple pharmacologicalactions. Currently, DADS has been well documented to ameliorate the testis injuries caused by X-rayirradiation[1??4]. However, the effect of DADS against heavy-ion-induced testis damage, particularly cell apoptosis,is still largely unknown. In this regard, based on ground experiments at accelerators, this study has been undertakento estimate the protective mechanisms of DADS against carbon ion-induced cell apoptosis at the level ofsignal transduction pathway in mouse testis.展开更多
The flocculation behavior of ultrafine kaolinite suspension was investigated through settlement tests and FTIR method was employed to probe the adsorption mechanism of flocculant on kaolinite. The results show that th...The flocculation behavior of ultrafine kaolinite suspension was investigated through settlement tests and FTIR method was employed to probe the adsorption mechanism of flocculant on kaolinite. The results show that the maximum settling rate of kaolinite occurs at pH value of 3.33,which is close to the point of zero charge(PZC) of kaolinite (3.5). This result is in good agreement with the double electric layer theory. Kaolinite suspension reaches the largest settling rate at a low concentration of 39 g/t for poly diallyl-dimethyl-ammonium chloride(PDADMA) flocculant,whereas for polyacrylamides(PAM) the dosage is required to be 500 g/t. When macromolecule polymer is adsorbed on surface,kaolinite particles may be flocculant due to the bridging effect. There are cation flocculant characteristic bands on the spectrum of kaolinite but no obvious shifting. Thus,the adsorption of poly diallyl-dimethyl-ammonium chloride on kaolinite surface is physical adsorption.展开更多
AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis.METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection....AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis.METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection.Liver energy metabolism was assessed in terms of lactate,pyruvate,lactate/pyruvate,ATP levels,lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) activities.In addition,membrane disintegration of the liver cells was evaluated by measuring lipid-peroxidation products,measured as malondialdehyde (MDA); nitric oxide (NO) levels; glucose-6-phosphatase (G6Pase),catalase (CAT) and superoxide dismutase (SOD) activities.Liver DNA level,glutathione-S-transferase (GST) and cytochrome c oxidase activities were used as DNA fragmentation indices.Aldose reductase (AR) activity was measured as an index for cancer cells resistant to chemotherapy and histopathological examination was performed on liver sections from different groups.RESULTS: NDEA significantly disturbed liver functions and most of the aforementioned indices.Treatment with DAS significantly restored liver functions and hepatocellular integrity; improved parameters of energy metabolism and suppressed free-radical generation.CONCLUSION: We provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumorigenesis caused by NDEA,as well as improving cancer-cell sensitivity to chemotherapy.This is mediated through combating oxidative stress of free radicals,improving the energy metabolic state of the cell,and enhancing the activity of G6Pase,GST and AR enzymes.展开更多
Problems associated with water eutrophication due to high phosphorus concentrations and related environmentally safe solutions have attracted wide attention.A novel bis(diallyl alkyl tertiary ammonium salt)polymer,par...Problems associated with water eutrophication due to high phosphorus concentrations and related environmentally safe solutions have attracted wide attention.A novel bis(diallyl alkyl tertiary ammonium salt)polymer,particularly poly(N1,N1,N6,N6-tetraallylhexane-1,6-diammonium dichloride)(PTAHDADC),was synthesized and characterized by Fourier transform infrared spectroscopy,nuclear magnetic resonance,scanning electron microscopy,mercury intrusion method,and thermogravimetric analysis.The adsorption characteristics in phosphorus were evaluated in dilute solution,and the recycling properties of PTAHDADC were investigated.Results showed that PTAHDADC possessed macropores with a size distribution ranging from 30 to 130μm concentrating at 63μm in diameter and had 46.52%of porosity,excellent thermal stability below 530 K,and insolubility.PTAHDADC could effectively remove phosphorus at p H=7–11 and had a removal efficiency exceeding 98.4%at pH=10–11.The adsorption equilibrium data of PTAHDADC for phosphorus accorded well with the Langmuir and pseudo-second-order kinetic models.Maximum adsorption capacity was 52.82 mg/g at 293 K.PTAHDADC adsorbed phosphorus rapidly and reached equilibrium within 90 min.Calculated activation energy Eawas 15.18 k J/mol.PTAHDADC presented an excellent recyclability with only 8.23%loss of removal efficiency after five adsorption–desorption cycles.The morphology and structure of PTAHDADC slightly changed as evidenced by the pre-and post-adsorption of phosphorus,but the process was accompanied by the partial deprotonation of the(–CH2)3-NH+group of PTAHDADC.The adsorption was a spontaneous exothermic process driven by entropy through physisorption,electrostatic attraction,and ion exchange.Survey results showed that PTAHDADC was a highly efficient and fast-adsorbing phosphorus-removal material prospective in treating wastewater.展开更多
基金supported by UGC-DAE-CSR,Kolkata(Grant No.:KC/CRS/19/RB-04/1047).
文摘Breast cancer is one of the leading causes of cancer-related deaths in women worldwide.It is a cancer that originates from the mammary ducts and involves mutations in multiple genes.Recently,the treatment of breast cancer has become increasingly challenging owing to the increase in tumor heterogeneity and aggressiveness,which gives rise to therapeutic resistance.Epidemiological,populationbased,and hospital-based case-control studies have demonstrated an association between high intake of certain Allium vegetables and a reduced risk in the development of breast cancer.Diallyl disulfide(DADS)and diallyl trisulfide(DATS)are the main allyl sulfur compounds present in garlic,and are known to exhibit anticancer activity as they interfere with breast cancer cell proliferation,tumor metastasis,and angiogenesis.The present review highlights multidrug resistance mechanisms and their signaling pathways in breast cancer.This review discusses the potential anticancer activities of DADS and DATS,with emphasis on drug resistance in triple-negative breast cancer(TNBC).Understanding the anticancer activities of DADS and DATS provides insights into their potential in targeting drug resistance mechanisms of TNBC,especially in clinical studies.
基金Supported by Fund for Science and Technology Program of Shaanxi Province,China,No.2010K01-141
文摘AIM:To investigate the effects of diallyl trisulfide(DATS),a garlic-derived organosulfur compound,in pancreatic cancer cells.METHODS:Human pancreatic cancer cells with wildtype p53 gene(Capan-2)and normal pancreatic epithelial cells(H6C7)were cultured in RPMI1640.DATS was prepared at a concentration of 100μmol/L.Cell viability was determined via the methyl thiazolyl tetrazolium assay.Apoptotic cells were detected by TUNEL assay.Cell cycle analysis was performed using flow cytometry.Protein expression was determined by Western blot.Bax and Bcl-2 expression was detected by immunofluorescence.Apoptosis genes and cell cycle were assessed by quantitative real-time polymerase chain reaction.RESULTS:DATS suppressed the viability of cultured human pancreatic cancer cells(Capan-2)by increasing the proportion of cells in the G2/M phase and induced apoptotic cell death.Western blot analysis indicated that DATS enhanced the expression of Fas,p21,p53and cyclin B1,but downregulated the expression of Akt,cyclin D1,MDM2 and Bcl-2.DATS induced cell cycle inhibition which was correlated with elevated levels of cyclin B1 and p21,and reduced levels of cyclin D1 in Capan-2 cells and H6C7 cells.DATS-induced apoptosis was markedly elevated in Capan-2 cells compared with H6C7 cells,and this was correlated with elevated levels of cyclin B1 and p53,and reduced levels of Bcl-2.DATS-induced apoptosis was correlated with downregulation of Bcl-2,Akt and cyclin D1 protein levels,and up-regulation of Bax,Fas,p53 and cyclin B protein levels in Capan-2 cells.CONCLUSION:DATS induces apoptosis of pancreatic cancer cells(Capan-2)and non-tumorigenic pancreatic ductal epithelial cells(H6C7).
文摘Aim: To investigate the protective effect of diallyl sulfide (DAS), a constituent of garlic, against testosterone-induced oxidative stress in male Swiss albino mice. Methods: The animals were given low (250 mg/animal) and high dose (500 mg/animal) of DAS in corn oil for 7 days along with testosterone (5 mg/kg body weight, i.p.). At the end of the study period, the prostate and the liver were dissected to determine various antioxidant enzyme levels (catalase, superoxide dismutase, glutathione reductase, glutathione-s-transferase) and lipid peroxidation. Results: In testosterone treated mice, depleted antioxidant enzyme level was accompanied with enhancement in lipid peroxidation in prostate and liver. DAS significantly restored the testosterone-induced antioxidant enzymes and lipid peroxidation in the both organs. These changes appear to be mediated by the antioxidant-enhancing effects of DAS. Conclusion: The results of the present study suggest that DAS is effective in exerting antioxidant effects by inhibiting testosterone-induced oxidative stress and might be helpful in preventing prostate cancer.
基金supported by a grant from Natural Science Foundation of Hubei Province of China (No. 2008CBD112)
文摘The inhibitory effects of diallyl sulfide(DAS) derived from allicin on in vitro and in vivo proliferation of human osteosarcoma MG-63 cells and the action mechanism,and the influence of DAS on invasive capability of MG-63 cells were investigated in order to search for the novel medicines for osteosarcoma.In the in vitro experiment,MG-63 cells were treated with different concentrations of DSA,and the morphological changes of MG-63 cells were observed under an inverted phase microscope.MTT method was used to assay the proliferation of MG-63 cells.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) was used to detect the VEGF mRNA expression level in MG-63 cells.By using Transwell invasion assay,the influence of DAS on invasive ability of MG-63 cells was tested.In the in vivo experiment,the nude mice MG-63 cells tumor-bearing model was established,and different concentrations of DAS were injected beside the tumor.Twenty-one days after treatment,the mice were killed,the tumor size and tumor inhibition rate were calculated.The microvessel density(MVD) was determined by using immunohistochemistry.In the in vitro experiment,different concentrations of DAS could obviously inhibit proliferation of MG-63 cells in a time-and concentration-dependent manner.RT-PCR revealed that the expression levels of VEGF mRNA in DSA groups(different concentrations) were significant reduced as compared with those in control group(all P<0.05).Transwell invasion assay indicated that in 20 and 40 μg/mL DAS groups,the number of migratory cells was 91.4±8.3 and 81.8±7.4 respectively,which was significantly declined as compared with that in control group(150.4±14.7,both P<0.05).In the in vivo experiment,DAS could significantly suppress the growth of MG-63 tumor-bearing tissue.Immunohistochemistry demonstrated that different concentrations(20 and 40 μg/mL) of DAS could significantly decrease MVD of MG-63 tumor-bearing tissue(all P<0.05).It was suggested that DAS could inhibit the growth of MG-63 cells probably by suppressing the expression of VEGF mRNA.
文摘It has been reported that diallyl sulfide (DAS), a sulfur-containing volatile compound in garlic (Allium sativum ), exerts anticarcinogenic activity in various rodent tumor models. In the present study, the antitumor property of DAS was tested in Swiss albino mice in the two steqe initiation-promotion mouse skin carcinogenesis. Skin cancers were initiated topically with a single subcarcinOgenic dose (52μg) of 7, 12-dimethyl benz (a) anthracene (DMBA). Promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5μg/animal for 32 weeks. DAS was applied topically (250μg/animal) thrice weekly for 3 weeks for anti-initiating and 1 h prior to each promotion treatment for anti-promoting studies. The results showed that the treatment schedule of DAS can effectively delay the onset of tumorigenesis and reduce the cumulative number of tumors and the average number of tumors per mouse. In groups in which DAS applied prior to initiation or promotion, a significant population of the aniinals remained tumor-free till the termination of experiment. These findings suggest that DAS can effectively inhibit chemically induced mouse skincarcinogenesis.
基金supported by grants from the Natural Science Foundation of Hubei Province (No. 2011CDB196)
文摘The protective effects of diallyl trisulfide on liver were examined in rats with sepsis. Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-six male Wistar rats were randomly divided into sham-operated group (group S, n=8), sepsis model group (group C, n=24), diallyl trisulfide (DATS)-treated group (group D, n=24). Animals in groups C and D were further divided into three subgroups according to different observation time points, with 8 rats in each sub-group.Rats in group D and C were intravenously injected with normal saline or DATS respectively at a dose of 20 mg/kg after the establishment of sepsis model. Eight rats in groups C and D were sacrificed at 3, 6 and 24 h post-CLP and their livers were harvested for detection of interleukin (IL)-1 receptor associated kinase-4 (IRAK-4), nuclear factor-κB (NF-κB), c-fos, c-jun, malondialdehydethhe (MDA) and superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α) and for pathological examination. The results showed that the levels of serum IRAK-4, NF-κB and TNF-α in hepatic tissues were higher in group C than group S (control group) (P<0.05). After DATS treatment, the levels of IRAK-4 and NF-κB in the hepatic tissues and serum TNF-α in group D were lower than those in group C (P<0.05). The levels of c-fos and c-jun and MDA in the hepatic tissues were higher in group C than in group S (P<0.05). After DATS treatment, the levels of c-fos and c-jun and MDA in the hepatic tissues were significantly lower in group D than in group C (P<0.05). When compared with group S group, concentration of SOD in the hepatic tissues in group C was significantly lower (P<0.05). After DATS treatment, the concentration of SOD in the hepatic tissues was higher in group D than in group C (P<0.05). These findings suggested that treatment with DATS could ameliorate sepsis-induced liver injury in rats. The protective effect might be related to its ability to inhibit the signal pathway of IRAK-4 and NF-κB, thereby decreasing the production of oxygen free radicals and down-regulating the expression of c-fos and c-jun.
文摘At high concentration (50 μg/ml), diallyl trisulfide (DATS) had an inhibitory effect on T cell activation (compared with control group, P<0.05). But at appropriate concentrations(3.125-12. 5 μg/ml). DATS augmented the activation of T lymphocytes by Con A (compared with control group, P<0. 01). The augmentation of T cell activation by DATS was related to its inhibitory effect on the production of nitric oxide (NO) by macrophages.In a wide range of concentrations (1-100 μg/ml) , DATS can inhibit the production of NO by macrophas,es (P<0.05,P<0.01). In addition, DATS can antagonize the inhibition of tumor-derived immunosuppressive factors produced by S180 cells and Ehrlich ascitic cancer cells on the activation of T cells, and reduce the inhibitory rate significantly (P<0.01). DATS, despite its inhibition of the production of NO by macrophages, can significantly enhance the production of hydrogen peroxide (H2O2 by macrophages.When macrophages were pretreated with DATS for 24 h, the cytotoxicity % of macrophages to three tumor cell lines was significantly higher than that in corresponding control group (P<0.05,P<0.01). In the presence of both DATS and LPS, the cytotoxicity of macrophages was further enhanced so that the cytotoxicity % of macrophages to tumor cells was significantly higher than either that in the presence of DAIS alone or that in the presence of LPS alone(P<0.05, P<0.01). These results indicate that DATS can augment the activation of T cells and enhance the anti-tumor function of macrophage, suggesting that DATS may be potentially useful in tumor therapy.
文摘Objective To explore the production and cytotoxicity of the reactive oxygen species(ROS)induced by diallyl trisulfid(DATS)in HL-60 cells.Methods HL-60 cells were either treated with various doses of DATS alone,or DATS combination with Apocynin,a specific NADPH oxidase inhibitor,or with antioxidant N-acetyl-L-cysteine(NAC)for 0,1,3,6,12 and 24 hours,respectively.The intracellular ROS level was measured by flow cytometry.The activity of NADPH oxidase was evaluated by NBT reduction experiment.The content of both malondialdehyde(MDA)and the protein carbonyl was analyzed by spectrophotometer.Results The results from flow cytometry indicated that DATS significantly increased the intracellular ROS level in HL-60 cells(P<0.05),which is a dose-and time-dependent.The fluorescence intensities of ROS reached at maximuam when HL-60 cells were incubated with 150 μmol·L-1 DATS for 3 hours.The NBT reduction experiment showed that DATS activated NADPH oxidase which had highest activity when cell were exposed to 150 μmol·L-1 DATS for 3 hours.Results DATS induced MDA and protein carbonyl production in HL-60 cells.Furrthermore,both MDA and protein carbonyl in the cells exposed to 150 μmol·L-1 DATS for 3 hours reached the highest level.Apocynin and NAC could attenuate the production of MDA and protein carbonyl,which suggested that ROS induced by DATS was involved in the toxicity to cells.Conclusions DATS induce ROS production through activating NADPH oxidase in HL-60 cells.ROS induced by DATS increase the oxidation of the membrane lipid and the protein of HL-60 cell.
文摘Objective To explore the effect and mechanism of diallyl trisulfide on the activity of NADPH oxidase in Hl-60 cells.Methods HL-60 cells were treated with DATS at a indicated concentration for 0,1,3,6,12 hours,respectively.The activity of NADPH oxidase was measured by the reduction of the yellow dye nitroblue tetrazolium(NBT).The mRNA expression of NADPH oxidase subunits,including gp91phox,p47 phox,p22 phox,Rac2 and Rac1,was detected by RT-PCR.The protein expression of p67 phox,gp91 phox and Rac2 was analyzed by Western blot.The cell membrane fractions were prepared according to the instruction of Mem-PER kit from Pierce Corp.Results The results showed that reduction ability of HL-60 cells for NBT markedly increased in a concentration-dependent manner following DATS incubation for 3 and 6 hours(P<0.05).HL-60 cells treated by DATS at a concentration of 150 μM for 3 hours have a maximal reduction effect for NBT.The results from RT-PCR indicated that mRNA expression of NADPH oxidase subunits,including p47phox,gp91 phox,p22 phox,Rac2 and Rac1,significantly increased in a concentration-dependent manner in HL-60 cells treated by DATS.The results from western blot showed that HL-60 cells following DATS incubation have a higher level expression of Rac2 and gp91phox,compared with untreated-HL-60 cells.Our results also indicated that a maximal expression level of p47phox,gp91 phox,p22 phox,Rac2 and Rac1in HL-60 cells is present at 3 hours following DATS incubation.We found that levels of both Rac2 and p67phox was reduced in the cytosolic fraction and meanwhile increased in the membrane fraction following HL-60 exposed to DATS,Which is dependent on the concentration and time of DATS treatment.Furthermore,the level of both Rac2 and p67phox located to the plasma membrane translocation was maximized following 150 μM of DATS incubation for 3 hours.Conclusions DATS induce the activation of NADPH oxidase by both up-regulating the expression of NADPH oxidase subunit and translocating the cytosolic Rac2 and p67 phox subunit to the plasma membrane in HL-60 cells.
文摘Mosl of anticancer drugs are mutagenic. A possible exeeption is diallyl .trisulfide(DAT ), a component of garlic. It is an antimutagenic anticunccr chemical although it ismainly uscd as antibiotic. Its modifying effeci on induction of UDS by mutagenicmitomycin C (MMC), cyclophosphamide (CP) and cis-diamine dichloroplatin (DDP) was invcstigiltcd with the UDS assay in the primary cultures of Wistar rat hepatocytes (hpc)using the autoradiographic technique. Resultsshowed that 1.0-4.0 nmol/ml of DAT didnot inducc UDS and that MMC, CP and DDP resulted in a significant induction ofdosc-dependent UDS. DAT enhanced induction of UDS by these drugs. A dose-effectrclationship was observed betwecn dose of DAT and enhancement of induction of UDS.Howcvcr, thc mcchanism of the enhancement is not clear.
基金This project is supported by the National Natural Science Foundation of China
文摘A new monomer, 3,9-diallyl-3, 9-dibenzyl-1, 5,7,11 - tetraoxa- spiro [5,5] undecane (6) was prepared by the reaction of 2- allyl- 2' - benzyl- propanediol - 1.3 with dibutyltin oxide, and then treated with CS_2. Monomer 4 could be initiated by cationic initiators to give a viscous polymer (white powder in the case of polymerization at 0℃). Upon the NMR and IR spectra of the obtained polymer, the components and their relative amount were estimated. The polymerization mechanism was discussed.
基金Key Program of National Natural Science Foundation of China (U1432248), National Natural Science Founda-tion of China (11175222, 11205219) , Western Talent Program of Chinese Academy of Sciences (Y260230XB0)
文摘Diallyl Disulfide (DADS) is the main organosulfur component of garlic and it is known for multiple pharmacologicalactions. Currently, DADS has been well documented to ameliorate the testis injuries caused by X-rayirradiation[1??4]. However, the effect of DADS against heavy-ion-induced testis damage, particularly cell apoptosis,is still largely unknown. In this regard, based on ground experiments at accelerators, this study has been undertakento estimate the protective mechanisms of DADS against carbon ion-induced cell apoptosis at the level ofsignal transduction pathway in mouse testis.
基金Project(2005CB623701) supported by the Major State Basic Research Development Program of China
文摘The flocculation behavior of ultrafine kaolinite suspension was investigated through settlement tests and FTIR method was employed to probe the adsorption mechanism of flocculant on kaolinite. The results show that the maximum settling rate of kaolinite occurs at pH value of 3.33,which is close to the point of zero charge(PZC) of kaolinite (3.5). This result is in good agreement with the double electric layer theory. Kaolinite suspension reaches the largest settling rate at a low concentration of 39 g/t for poly diallyl-dimethyl-ammonium chloride(PDADMA) flocculant,whereas for polyacrylamides(PAM) the dosage is required to be 500 g/t. When macromolecule polymer is adsorbed on surface,kaolinite particles may be flocculant due to the bridging effect. There are cation flocculant characteristic bands on the spectrum of kaolinite but no obvious shifting. Thus,the adsorption of poly diallyl-dimethyl-ammonium chloride on kaolinite surface is physical adsorption.
文摘AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis.METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection.Liver energy metabolism was assessed in terms of lactate,pyruvate,lactate/pyruvate,ATP levels,lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) activities.In addition,membrane disintegration of the liver cells was evaluated by measuring lipid-peroxidation products,measured as malondialdehyde (MDA); nitric oxide (NO) levels; glucose-6-phosphatase (G6Pase),catalase (CAT) and superoxide dismutase (SOD) activities.Liver DNA level,glutathione-S-transferase (GST) and cytochrome c oxidase activities were used as DNA fragmentation indices.Aldose reductase (AR) activity was measured as an index for cancer cells resistant to chemotherapy and histopathological examination was performed on liver sections from different groups.RESULTS: NDEA significantly disturbed liver functions and most of the aforementioned indices.Treatment with DAS significantly restored liver functions and hepatocellular integrity; improved parameters of energy metabolism and suppressed free-radical generation.CONCLUSION: We provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumorigenesis caused by NDEA,as well as improving cancer-cell sensitivity to chemotherapy.This is mediated through combating oxidative stress of free radicals,improving the energy metabolic state of the cell,and enhancing the activity of G6Pase,GST and AR enzymes.
基金supported by the Scientific Research Fund of Hunan Education Department (No. 16A069)the National Nature Science Foundation of China (No. 51378201)
文摘Problems associated with water eutrophication due to high phosphorus concentrations and related environmentally safe solutions have attracted wide attention.A novel bis(diallyl alkyl tertiary ammonium salt)polymer,particularly poly(N1,N1,N6,N6-tetraallylhexane-1,6-diammonium dichloride)(PTAHDADC),was synthesized and characterized by Fourier transform infrared spectroscopy,nuclear magnetic resonance,scanning electron microscopy,mercury intrusion method,and thermogravimetric analysis.The adsorption characteristics in phosphorus were evaluated in dilute solution,and the recycling properties of PTAHDADC were investigated.Results showed that PTAHDADC possessed macropores with a size distribution ranging from 30 to 130μm concentrating at 63μm in diameter and had 46.52%of porosity,excellent thermal stability below 530 K,and insolubility.PTAHDADC could effectively remove phosphorus at p H=7–11 and had a removal efficiency exceeding 98.4%at pH=10–11.The adsorption equilibrium data of PTAHDADC for phosphorus accorded well with the Langmuir and pseudo-second-order kinetic models.Maximum adsorption capacity was 52.82 mg/g at 293 K.PTAHDADC adsorbed phosphorus rapidly and reached equilibrium within 90 min.Calculated activation energy Eawas 15.18 k J/mol.PTAHDADC presented an excellent recyclability with only 8.23%loss of removal efficiency after five adsorption–desorption cycles.The morphology and structure of PTAHDADC slightly changed as evidenced by the pre-and post-adsorption of phosphorus,but the process was accompanied by the partial deprotonation of the(–CH2)3-NH+group of PTAHDADC.The adsorption was a spontaneous exothermic process driven by entropy through physisorption,electrostatic attraction,and ion exchange.Survey results showed that PTAHDADC was a highly efficient and fast-adsorbing phosphorus-removal material prospective in treating wastewater.