Synthesis of novel 3-allylseleno-6-alkylthiopyridazines: their anticancer activity against MCF-7 cells

A new series of 3-allylseleno-6-alkylthiopyridazines 6a–6g was synthesized by two synthetic routes from 3,6-dichloropyridazine to develop new anticancer agents. These new compounds showed antiproliferative activities against breast cancer (MCF-7) cells in CCK-8 assays, and could be promising candidates for chemotherapy of carcinomas. Compound 6e (3-allylseleno-6-pentylthiopyridazine) showed higher potency than 5FU for inhibiting the growth of these cell lines. This suggests the potential anticancer activity of compound 6e.     

Design, synthesis, and antiproliferative activity of 3,4-diarylpyrazole-1-carboxamide derivatives against melanoma cell line

Synthesis of a new series of 3,4-diarylpyrazole-1-carboxamide derivatives is described. Their antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The biological results indicated that five synthesized compounds (Ig, Ii, IIc, IIg, and IIh) exhibited similar activity to Sorafenib. In addition, three compounds (IIa, IIb, and IIi) were more potent than Sorafenib. Among all of these derivatives, compound IIa which has dimethylamino and phenolic moieties showed the most potent antiproliferative activity against A375P human melanoma cell line. Virtual screening was carried out through docking of the most potent compound IIa into the domain of V600E-b-Raf and the binding mode was studied.     

5-氟尿嘧啶类衍生物的设计、合成及其抗肿瘤活性研究

目的合成一系列含5-氟尿嘧啶(5-FU)结构的衍生物并对此类化合物进行抗肿瘤活性研究。方法以5-FU为起始原料,通过加成、缩合,与邻硝基苯氧乙酸类载体通过酯化反应得到目标化合物,并用1H-NMR和MS确证其结构。MTT法检测目标化合物对细胞A549、Hep G 2、He La和正常细胞WI-38的抑制作用。结果目标化合物对肿瘤细胞均有一定的抑制活性,尤其是化合物9对细胞A549的抑制作用[IC50=(3.04±0.48)μmol·L-1]明显优于阳性对照5-FU[IC50=(49.81±1.49)μmol·L-1],且对于正常细胞的毒副作用较小。结论该合成路线所需反应条件温和,便于操作,且目标化合物9具有较好的抗肿瘤活性,值得进一步研究。     

地塞米松预处理人乳腺癌MCF-7细胞对多西他赛抗肿瘤活性的影响

目的 探讨地塞米松预处理人乳腺癌MCF-7细胞后,对化疗药物多西他赛(艾素)抗肿瘤活性的影响.方法 以不同浓度(1×10-8～1×10-6 mol·L-1)的地塞米松预先作用于人乳腺癌MCF-7细胞后,再以艾素(5×10-6 mol·L-1)处理,在以上药物作用的相应时间段,通过流式细胞仪技术测定细胞凋亡,采用细胞计数观察细胞生长密度、形态.结果 地塞米松对MCF-7细胞增殖有抑制作用(P＜0.01),艾素能够明显抑制MCF-7细胞增殖,促进其凋亡(P＜0.01),地塞米松预处理后艾素干预MCF-7细胞的增殖抑制作用较单用艾素减弱(P＜0.01),且随地塞米松浓度的增加,其对化疗药艾素的凋亡抑制作用的影响增强.结论 地塞米松预处理对艾素诱导的人乳腺癌MCF-7细胞的凋亡具有明显的阻抑作用,抑制了多西他赛的抗肿瘤活性.     

人乳腺癌细胞株MCF-7及其紫杉醇耐药株中紫杉醇结合的差异蛋白质分析

目的分析人乳腺癌细胞株MCF-7及其紫杉醇耐药株MCF-7/Taxol中的紫杉醇结合的差异蛋白质,探索抗肿瘤药物新靶点。方法合成生物素化紫杉醇,HPLC-MS联用法检测合成产物。SRB法检测生物素化紫杉醇的生物活性,免疫磁珠偶联后与MCF-7及其MCF-7/Taxol的全细胞蛋白液反应,获得紫杉醇结合蛋白,SDS-PAGE电泳获得差异蛋白条带,LC-MS/MS分析,Western blot鉴定差异结合蛋白。结果成功合成生物素化紫杉醇,生物素化紫杉醇的生物活性和紫杉醇相当。经过蛋白电泳分析,MCF-7/Taxol的紫杉醇结合蛋白较MCF-7多一差异条带,LC-MS/MS分析提示数个目标蛋白,经过Western blot验证差异条带中有Heat shock protein HSP90、Dermcidin Precursor、Actinin。结论成功获得了MCF-7和MCF-7/Taxol之间的紫杉醇细胞差异结合蛋白,对这些蛋白作用机制的的深入探索,可能为抗肿瘤药物的研究寻找到新的靶点蛋白,发现新的肿瘤耐药机制。     

Ferrocene incorporated PAMAM dendrons: synthesis, characterization, and anti-cancer activity against AGS cell line

Novel series of asymmetric Poly(amidoamine) (PAMAM) dendrons containing a single ferrocene unit located as the focal point has been prepared. First, second, and third generation ferrocene-PAMAM dendrons with branched amine periphery and focal ferrocene functionality were synthesized via divergent pathways. The synthesized dendrons were characterized by FT-IR and NMR spectroscopy. Real-time cell analysis, cell viability, and anti-cancer activity of ferrocene-PAMAM dendrons were evaluated in AGS cells. While cell viability decreased, anti-cancer activity increased gradually in a dose-dependent manner in one, two, and three generations.     

Synthesis, characterization, anticancer, and antioxidant activity of some new thiazolidin-4-ones in MCF-7 cells

There are limited studies centring on the potential of thiazolidin-4-ones as anticancer agents. In this study, a new series of 2-(3-substituted-1H-pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-4-one (4a–o) have been synthesized by cyclo-condensation reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4-triazole-3-thione (3a–o) and thioglycolic acid. The structures of all the synthesized compounds were confirmed by elemental analysis, spectral techniques like IR, ¹H NMR, and mass spectroscopy. Few compounds exhibited dose-dependent cytotoxic effect in MTT assay in human breast cancer (MCF-7) cells. Apoptotic degradation of DNA due to action of potent thiazolidin-4-ones was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). A concentration-dependent increase in tail length and olive tail moment was observed when treated with thiazolidin-4-ones. In vitro antioxidant studies like DPPH and ABTS-free radical scavenging assays-indicated moderate activity of thiazolidin-4-ones.     

The effect of leucovorin on the synthesis of methotrexate poly-gamma-glutamates in the MCF-7 human breast cancer cell line

The modulating effects of leucovorin on the synthesis of methotrexate (MTX) polyglutamates in the MCF-7 human breast cancer cell line have been investigated using a paired-ion high performance liquid chromatography (HPLC) system. Leucovorin decreased the intracellular level of MTX and profoundly affected polyglutamate synthesis irrespective of whether it was administered with or after MTX. Inhibition of MTX polyglutamate synthesis was also observed when concentrations of leucovorin too low to affect intracellular levels of MTX were employed. Leucovorin did not promote efflux of MTX from the MCF-7 cells and did not affect the distribution of the retained drug amongst the various polyglutamate forms.     

三氧化二砷诱导乳腺癌细胞株MCF-7凋亡对端粒酶活性的影响

<正>乳腺癌是严重威胁妇女健康的恶性肿瘤之一,近年发病率逐年上升,且发病年龄也趋于年轻化。近年来研究发现As2O3不仅对APL细胞,而且对其他血液肿瘤细胞和许多实体瘤细胞均具有诱导凋亡作用。Wang等研究表明端粒酶与恶性肿瘤发生有着紧密的关联,p21特异性核苷     

抗人stathmin单克隆抗体及其联合紫杉醇对人乳腺癌细胞的生长抑制作用

目的：探讨抗人stathmin单克隆抗体、紫杉醇分别单用或联用对乳腺癌细胞系MCF-7的生长抑制及促凋亡作用。方法：以不同浓度的抗人stathmin单克隆抗体、紫杉醇分别组成单药组和联合用药组,另设不加药的空白对照组,分别作用于MCF-7细胞24、48、72、96h,观察细胞数量和形态的变化。MTT法检测单克隆抗体、紫杉醇单用组、联用组以及对照组对MCF-7细胞的增殖抑制作用,用流式细胞仪通过AnnexinV/PI双染法检测各组细胞凋亡率的改变。结果：不同浓度的各实验组作用后细胞数量明显减少、形态不规则,部分细胞核固缩和胞质减少,而对照组细胞生长状态良好。抗人stathmin单克隆抗体、紫杉醇单用与联用均能抑制MCF-7细胞增殖,呈剂量-时间依赖效应,联用组细胞抑制率较单药组明显增高,差异具有统计学意义（P〈0.05）,两药联用有交互效应（P〈0.05）。抗人stathmin单克隆抗体、紫杉醇单用与联用均能诱导MCF-7细胞凋亡,联合组更为明显（P〈0.05）。结论：抗人stathmin单克隆抗体、紫杉醇单用与联用均能抑制MCF-7细胞增殖,诱导其凋亡;两药联合作用于人乳腺癌MCF-7细胞具有协同作用。     

人乳腺癌细胞系MCF-7/W和MCF-7/ADM细胞中阿霉素结合蛋白的分析

目的通过比较野生型和耐药型人乳腺癌细胞系MCF-7中阿霉素(ADM)结合蛋白的差异,探讨耐药型MCF-7的多药耐药机制。方法酯化脱水法制备生物素化ADM,HPLC纯化,MS分析确证。以ADM耐药指数≥200的MCF-7细胞(MCF-7/ADM)和野生型MCF-7细胞(MCF-7/W)为研究材料,采用链亲和素-亲和甄别磁珠法从两种细胞全蛋白中分离出与ADM结合的蛋白。经SDS-PAGE,肽质谱指纹图谱(MALDI_TOF_MS)分析ADM结合蛋白的种类。细胞迁移实验比较MCF-7/W和MCF-7/ADM细胞的运动能力。结果生物素化ADM、ADM对MCF-7/W的IC50分别为0.796μmol.L-1和0.547μmol.L-1。分别从MCF-7/W和MCF-7/ADM中采用亲和甄别磁珠法获得ADM结合蛋白20种及17种,SDS-PAGE分析两者有一条差异条带,序列分析共同蛋白为myosin,beta-actin,alpha-actin,keratin。MCF-7/W和MCF-7/ADM细胞在培养72h后,前者的迁移速度较快。结论除了因方法学灵敏度限制未能解析的结合蛋白外,MCF-7细胞内的主要ADM结合蛋白是细胞骨架蛋白和参与细胞运动的蛋白。ADM与MCF-7细胞中的骨架蛋白结合后,对细胞的迁移运动有一定的影响作用。     

Design,synthesis and antibreast cancer MCF-7 cells biological evaluation of heterocyclic analogs of resveratrol

A new series of resveratrol heterocyclic analogs (4a–m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure–activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC₅₀ = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC₅₀ = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4′-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F₁-ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.     

Uv-c照射对MCF-7细胞PTEN表达及分布的影响

目的初步探讨人乳腺癌细胞MCF-7经Uv-c照射后PTEN表达及分布变化。方法利用流式细胞仪检测Uv-c照射后细胞周期改变;利用Westernblot检测Uv-c照射后PTEN表达变化,并且利用免疫荧光方法检测PTEN细胞分布变化。结果 UV-c照射前,细胞内PTEN主要分布于胞核周围的胞质中;UV-c照射MCF-7细胞后,使阻滞于细胞G2/M期,24后,细胞内总PTEN量明显增多,且主要均匀地分布在细胞质中。结论 Uv-c照射后,细胞处于周期阻滞状态,伴随着PTEN蛋白表达上调且部分蛋白发生浆核转位。     

Leccinum vulpinum Watling induces DNA damage,decreases cell proliferation and induces apoptosis on the human MCF-7 breast cancer cell line

The current work aimed to study the antitumour activity of a phenolic extract of the edible mushroom Leccinum vulpinum Watling, rich essentially in hydroxybenzoic acids. In a first approach, the mushroom extract was tested against cancer cell growth by using four human tumour cell lines. Given the positive results obtained in these initial screening experiments and the evidence of some studies for an inverse relationship between mushroom consumption and breast cancer risk, a detailed study of the bioactivity of the extract was carried out on MCF-7 cells. Once the selected cell line to precede the work was the breast adenocarcinoma cell line, the human breast non-malignant cell line MCF-10A was used as control.Overall, the extract decreased cellular proliferation and induced apoptosis. Furthermore, the results also suggest that the extract causes cellular DNA damage. Data obtained highlight the potential of mushrooms as a source of biologically active compounds, particularly with antitumour activity.     

The influence of lycopene on the proliferation of human breast cell line (MCF-7).

Lycopene, a non-provitaminic carotenoid, present in many fruit and vegetables, such as tomatoes and their processed products, has been associated with decreased risk of chronic diseases including cancer. The influence of lycopene on the proliferation of the breast tumour cell line (MCF-7) was tested using MTT and BrdU assays at different time intervals (from 24 to 72h) and dose-response (from 0.125 to 100muM). The induction of Gap Junction Intercellular Communication (GJIC) was evaluated by dye-transfer assay using Lucifer Yellow on monolayer cells treated with different lycopene concentrations (from 0.125 to 5muM) for 6 to 48h. The Minimal Inhibitory Concentration (MIC) of lycopene was of 5muM, after a 24h exposure. A prolonged exposure time (72h) induced a similar inhibitory effect. Lycopene stimulated the functionality of GJIC at concentrations of 1muM after 24h and this effect was dose-dependent. The induction of GJIC by lycopene was confirmed by an increased expression of connexin 43. Collectively, the above data confirm the inhibitor effects of lycopene on MCF-7 cell growth and suggest that lycopene is involved in the modulation of the gap junction intercellular communication in this cell line, as observed for other cancer cell lines.