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
Diallyl disulfide was synthesized by phase transfer catalyst （PTC） during microwave irradiation. The effects of different factors, such as the power of microwave irradiation, the time of microwave irradiation, PTC r...Diallyl disulfide was synthesized by phase transfer catalyst （PTC） during microwave irradiation. The effects of different factors, such as the power of microwave irradiation, the time of microwave irradiation, PTC reagents amount and the mole ratio of reactants, on the yield of product were investigated. The structure of diallyl disulfide was characterized by infrared spectra, mass spectra and ^1 H nuclear magnetic resonance. The bioactivity of diallyl disulfide was evaluated by cell viability assay on HepG2 hepatoma cells. The results show that the optimal reaction conditions are as follows： tetrabutylammonium bromide（TBAB） selected as a PTC, the mass ratio of TBAB to sodium disulfide of 0.021 ： 1, the power of irradiation of 195 W, the reaction time of 12 rain, and the mole ratio of sodium disulfide to allyl chloride of 0.65 ： 1. The yield of diallyl disulfide is 82.2%. The synthetical diallyl disulfide appears to be cytotoxic to HepG2 heoatoma cells in a dose-dependent manner.展开更多
AIMS To assess the protective effect of diallyl disulfide (DADS) and its combined use with N-acetyl-cysteine (NAC) on acetaminophen (APAP) hepatotoxicity in C57BL/6N (B6) mice pretreated with β naphthoflavone (BN...AIMS To assess the protective effect of diallyl disulfide (DADS) and its combined use with N-acetyl-cysteine (NAC) on acetaminophen (APAP) hepatotoxicity in C57BL/6N (B6) mice pretreated with β naphthoflavone (BNF). METHODS B6 mice were divided into six groups and all compounds used were injected intraperitoneally. Except for control and APAP group (receiving APAP only), the other groups received an injection of APAP (350mg/kg) 48 hours after BNF (200mg/kg) and either of DADS (200mg/kg), or NAC (500mg/kg) or both DADS and NAC. DADS was given 2 hours before APAP and NAC was injected with APAP. The mean survival time was recorded and livers were examined histologically. Hepatic glutathione (GSH) levels and plasma ALT were also determined at different time points. To evaluate the effect of DADS or NAC on hepatic P450 induction by BNF, liver microsomes were prepared and 7 ethoxyresorufin O dealkylase (ERD) activity was determined using spectrofluorometrical methods. In vitro effect of DADS or NAC on ERD activity was assayed by directly incubating microsomal suspension with DADS or NAC of different concentrations. RESULTS APAP was not toxic to mice without BNF pretreatment, but caused severe liver necrosis and death of all BNF treated mice in 4 hours. A sharp depletion of GSH (approximately 62% of its initial content at 2 hours and 67% at 4 hours) and a linear elevation of ALT levels (536 8±29 5 Sigma units at 2 hours and 1302 5±74 9 at 4 hours) were observed. DADS and NAC given individually produced mild protection, resulting in prolonged survival, a slower decline of GSH level and a less steeper elevation of ALT level. All mice died eventually. Co administration of DADS and NAC completely protected mice. GSH level in this group lowered by about 35% and 30% at 2 and 4 hours, and ALT was 126±18 and 157 5±36 6 Sigma units at 2 and 4 hours. ERD activity in BNF treated mice was about 5 times that of the constitutive level determined in normal mice. Neither DADS nor NAC inhibited P450 1A1/1A2 induction as determined by their effect on the induction of ERD activity. In vitro assay indicates that DADS, but not NAC, was a potent inhibitor of ERD activity (IC 50 =4 6μM). CONCLUSIONS A combined use of both DADS and NAC produced full protection in BNF treated mice against APAP hepatotoxicity. The mechanism is that DADS inhibits P450 1A1/1A2 activity, but not induction, which substantially reduces production of NAPQI, while NAC enhances liver detoxifying capability via serving as a precursor of GSH and stimulating GSH synthesis.展开更多
目的观察二烯丙基二硫(DADS)在体内诱导胃癌细胞分化的作用及对人胃癌细胞移植瘤组蛋白乙酰化的影响。方法裸鼠皮下注入人胃癌细胞MGC803建立人胃癌异种移植模型,采用光学显微镜观察移植瘤细胞形态变化,流式细胞光度术和W estern b lot...目的观察二烯丙基二硫(DADS)在体内诱导胃癌细胞分化的作用及对人胃癌细胞移植瘤组蛋白乙酰化的影响。方法裸鼠皮下注入人胃癌细胞MGC803建立人胃癌异种移植模型,采用光学显微镜观察移植瘤细胞形态变化,流式细胞光度术和W estern b lot分析DADS对MGC803细胞移植瘤细胞周期分布的影响及瘤组织中p21WAF1蛋白、组蛋白H3、H4乙酰化的表达情况。结果腹腔注射DADS剂量为100、200 mg.kg-1时对移植瘤有明显生长抑制作用;光学显微镜显示经DADS处理后瘤细胞密度及异型性明显减小。流式细胞仪分析结果显示DADS呈浓度依赖性将移植瘤细胞阻滞在G2/M期。DADS浓度为100 mg.kg-1和200 mg.kg-1作用瘤细胞后,与对照组相比分别可使G2/M期细胞增加2.22和3.37倍。W estern b lot分析表明在G2/M期阻滞同时有组蛋白H3乙酰化表达增加,但组蛋白H4乙酰化表达水平不受DADS作用的影响;瘤组织中的p21WAF1蛋白表达量也随DADS浓度升高而上升。结论DADS对胃癌细胞裸鼠移植瘤的生长有明显抑制和诱导分化作用,这种抑制可能与其阻滞移植瘤细胞周期、上调瘤细胞组蛋白乙酰化及p21WAF1蛋白水平有关。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Project (C03050205) supported by the National Natural Science Foundation of China
文摘Diallyl disulfide was synthesized by phase transfer catalyst （PTC） during microwave irradiation. The effects of different factors, such as the power of microwave irradiation, the time of microwave irradiation, PTC reagents amount and the mole ratio of reactants, on the yield of product were investigated. The structure of diallyl disulfide was characterized by infrared spectra, mass spectra and ^1 H nuclear magnetic resonance. The bioactivity of diallyl disulfide was evaluated by cell viability assay on HepG2 hepatoma cells. The results show that the optimal reaction conditions are as follows： tetrabutylammonium bromide（TBAB） selected as a PTC, the mass ratio of TBAB to sodium disulfide of 0.021 ： 1, the power of irradiation of 195 W, the reaction time of 12 rain, and the mole ratio of sodium disulfide to allyl chloride of 0.65 ： 1. The yield of diallyl disulfide is 82.2%. The synthetical diallyl disulfide appears to be cytotoxic to HepG2 heoatoma cells in a dose-dependent manner.
文摘AIMS To assess the protective effect of diallyl disulfide (DADS) and its combined use with N-acetyl-cysteine (NAC) on acetaminophen (APAP) hepatotoxicity in C57BL/6N (B6) mice pretreated with β naphthoflavone (BNF). METHODS B6 mice were divided into six groups and all compounds used were injected intraperitoneally. Except for control and APAP group (receiving APAP only), the other groups received an injection of APAP (350mg/kg) 48 hours after BNF (200mg/kg) and either of DADS (200mg/kg), or NAC (500mg/kg) or both DADS and NAC. DADS was given 2 hours before APAP and NAC was injected with APAP. The mean survival time was recorded and livers were examined histologically. Hepatic glutathione (GSH) levels and plasma ALT were also determined at different time points. To evaluate the effect of DADS or NAC on hepatic P450 induction by BNF, liver microsomes were prepared and 7 ethoxyresorufin O dealkylase (ERD) activity was determined using spectrofluorometrical methods. In vitro effect of DADS or NAC on ERD activity was assayed by directly incubating microsomal suspension with DADS or NAC of different concentrations. RESULTS APAP was not toxic to mice without BNF pretreatment, but caused severe liver necrosis and death of all BNF treated mice in 4 hours. A sharp depletion of GSH (approximately 62% of its initial content at 2 hours and 67% at 4 hours) and a linear elevation of ALT levels (536 8±29 5 Sigma units at 2 hours and 1302 5±74 9 at 4 hours) were observed. DADS and NAC given individually produced mild protection, resulting in prolonged survival, a slower decline of GSH level and a less steeper elevation of ALT level. All mice died eventually. Co administration of DADS and NAC completely protected mice. GSH level in this group lowered by about 35% and 30% at 2 and 4 hours, and ALT was 126±18 and 157 5±36 6 Sigma units at 2 and 4 hours. ERD activity in BNF treated mice was about 5 times that of the constitutive level determined in normal mice. Neither DADS nor NAC inhibited P450 1A1/1A2 induction as determined by their effect on the induction of ERD activity. In vitro assay indicates that DADS, but not NAC, was a potent inhibitor of ERD activity (IC 50 =4 6μM). CONCLUSIONS A combined use of both DADS and NAC produced full protection in BNF treated mice against APAP hepatotoxicity. The mechanism is that DADS inhibits P450 1A1/1A2 activity, but not induction, which substantially reduces production of NAPQI, while NAC enhances liver detoxifying capability via serving as a precursor of GSH and stimulating GSH synthesis.
文摘目的观察二烯丙基二硫(DADS)在体内诱导胃癌细胞分化的作用及对人胃癌细胞移植瘤组蛋白乙酰化的影响。方法裸鼠皮下注入人胃癌细胞MGC803建立人胃癌异种移植模型,采用光学显微镜观察移植瘤细胞形态变化,流式细胞光度术和W estern b lot分析DADS对MGC803细胞移植瘤细胞周期分布的影响及瘤组织中p21WAF1蛋白、组蛋白H3、H4乙酰化的表达情况。结果腹腔注射DADS剂量为100、200 mg.kg-1时对移植瘤有明显生长抑制作用;光学显微镜显示经DADS处理后瘤细胞密度及异型性明显减小。流式细胞仪分析结果显示DADS呈浓度依赖性将移植瘤细胞阻滞在G2/M期。DADS浓度为100 mg.kg-1和200 mg.kg-1作用瘤细胞后,与对照组相比分别可使G2/M期细胞增加2.22和3.37倍。W estern b lot分析表明在G2/M期阻滞同时有组蛋白H3乙酰化表达增加,但组蛋白H4乙酰化表达水平不受DADS作用的影响;瘤组织中的p21WAF1蛋白表达量也随DADS浓度升高而上升。结论DADS对胃癌细胞裸鼠移植瘤的生长有明显抑制和诱导分化作用,这种抑制可能与其阻滞移植瘤细胞周期、上调瘤细胞组蛋白乙酰化及p21WAF1蛋白水平有关。
