小白菊内酯对大鼠血管平滑肌细胞增殖的影响及机制研究

目的:探讨小白菊内酯对血管平滑肌细胞增殖的影响及作用机制。方法:培养大鼠胸主动脉血管平滑肌细胞(VSMC),Western印迹杂交法检测c-fos,c-myc,p15,p16,p18,p19蛋白表达,流式细胞仪检测VSMC周期情况,[³H]TdR参入测定VSMC的DNA合成。结果:小白菊内酯以时间依赖关系抑制c-fos,c-myc蛋白表达,但不影响p15,p16,p18,p19蛋白表达,以剂量依赖关系使VSMC周期中的G₀/G₁期细胞比例明显增多,S期细胞比例显著减少,同时抑制VSMC的[³H]TdR参入。结论:小白菊内酯可能通过抑制c-fos,c-myc蛋白表达,而不是影响p15,p16,p18,p19蛋白表达来抑制VSMC增殖。     

小白菊内酯抑制紫杉醇诱导的肿瘤细胞凋亡

目的　探讨NF κB在紫杉醇诱导肿瘤细胞凋亡中的作用及小白菊内酯对紫杉醇诱导凋亡的影响。方法　以人乳癌BCap37细胞和人表皮KB细胞为研究对象 ,用 5,1 0和 2 0 μmol·L-1 小白菊内酯预处理细胞 ,以DNA凋亡梯状条带、DNA含量、MTT、细胞甩片及电泳迁移率变动分析 (EMSA)法检测它对紫杉醇诱导细胞凋亡的影响并探索其作用靶点。结果　通过检测DNA凋亡梯状条带、DNA含量和细胞生存率 ,2 0μmol·L-1 小白菊内酯能显著抑制紫杉醇所诱导的BCap37和KB细胞凋亡 ,但不影响紫杉醇诱导肿瘤细胞G2 /M期阻滞。EMSA实验表明小白菊内酯能抑制紫杉醇诱导激活NF κB。结论　小白菊内酯通过抑制NF κB的激活来抑制紫杉醇所诱导的肿瘤细胞凋亡 ,而紫杉醇诱导肿瘤细胞凋亡的过程可能与G2 /M期阻滞无关     

基于网络药理学及分子对接技术探讨小白菊内酯治疗肺癌的分子机制

目的 基于网络药理学和分子对接技术探究小白菊内酯治疗肺癌的分子机制。方法 从Swiss Target Prediction、SuperPred和HERB数据库筛选小白菊内酯的作用靶基因。通过GeneCards、OMIM、PharmGkb、TTD、DrugBank和DisGeNET数据库收集肺癌的疾病靶基因。使用Cytoscape软件构建“药物–靶基因–疾病”网络,利用STRING数据库构建蛋白互作网络（PPI）;通过Bioconductor平台进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）富集分析,利用分子对接技术确定小白菊内酯与核心靶基因结合作用。结果 小白菊内酯靶基因共88个,肺癌相关基因8 814个,取交集得到小白菊内酯–肺癌共同靶基因68个。在PPI网络中,组蛋白去乙酰化酶2(HDAC2)、细胞色素P450(CYP)2D6、CYP3A4、CYP2A6、前列腺素内过氧化物酶2(PTGS2)、Toll样受体4(TLR4)、溴结构域包含蛋白（BRD）2、BRD4、单胺氧化酶A(MAOA)、无嘌呤/无嘧啶核酸内切酶-1(APEX1)是小白菊内酯作用于肺癌的10个核心基因...     

Inhibitory Effects of Parthenolide on the Angiogenesis Induced by Human Multiple Myeloma Cells and the Mechanism

The inhibitory effects of parthenolide （PTL） on angiogenesis induced by multiple myeloma （MM） cells in vitro and the mechanism were investigated. Human MM line RPMI8226 cells were cultured in vitro. The effects of MM culture supernatant on the migration and tubule formation ability of human umbilical vein endothelial cells （HUVECs） treated with PTL were observed. By using Western blot, the expression of p65 and IкB-α in MM cells was detected. RT-PCR was used to assay the expression of VEGF, IL-6, MMP2 and MMP9 mRNA in MM cells. ELISA was used to measure the levels of VEGF and IL-6 in MM cell culture supernatant. The expression of MMP2 and MMP9 in MM cells was examined by immunohistochemistry. （1） In 3.5, 5.0, 7.5 and 10 μmol/L PTL groups the number of migrated cells was 310±56, 207±28, 127±21 and 49±10 respectively, which was significantly different from that in positive control group （598±47） （P〈0.01）. In 3.5 and 5.0 μmol/L PTL groups the areas of capillary-like structures were 0.092±0.003 and 0.063±0.002 mm2, significantly less than in positive control group （0.262±0.012 mm2） （P〈0.01）, but in 7.5 and 10 μmol/L PTL groups no capillary-like structures were found; （2） After treatment with different concentrations of PTL for 48 h, the expression of p65 protein was gradually decreased, while that of IкB-α was gradually enhanced with the increased concentration of PTL; （3） After treatment with 3.5, 5.0, 7.5 and 10 μmol/L PTL for 48 h, the VEGF levels in the supernatant were 2373.4±392.2, 1982.3±293.3, 1247.0±338.4 and 936.5±168.5 pg/mL respectively, significantly different from those in positive control group （2729±440.0 pg/mL） （P〈0.05）. After treatment with 7.5 and 10 μmol/L PTL, the IL-6 levels in the culture supernatant were 59.6±2.8 and 41.4±9.8 pg/mL respectively, signifi- cantly lower than in positive control group （1287.3±43.5 pg/mL） （P〈0.05）; （4） RT-PCR revealed that PTL could significantly inhibit the expression of V     

Cell context-dependent activities of parthenolide in primary and metastatic melanoma cells

Background and purpose:

Growing evidence implicates NF-κB as an important contributor to metastasis and increased chemoresistance of melanoma. Here, we report the effects of parthenolide on either untreated, cisplatin- or TNFα-treated melanoma cell lines A375, 1205Lu and WM793, exhibiting different levels of constitutive NF-κB activity.

Experimental approach:

Electrophoretic mobility shift assay was used to assess changes in NF-κB activity, and real-time PCR to evaluate expression of NF-κB-regulated genes. Cell cycle arrest and apoptosis were assessed by flow cytometry. Cell death was also visualized by fluorescence microscopy. Migration was determined by scratch assay and invasiveness by Matrigel assay.

Key results:

Parthenolide suppressed both constitutive and induced NF-κB activity in melanoma cells. This was accompanied by down-regulation of cancer-related genes, with NF-κB-binding sites in their promoters, including: Bcl-X_L, survivin, cyclin D1, interleukin 8 and matrix metalloproteinase 9. When the various effects of 6 µM parthenolide were compared, apoptosis associated with loss of mitochondrial membrane potential was most efficiently induced in 1205Lu cells, cell cycle arrest in G₀/G₁ phase was observed in WM793 cells, and high metastatic potential was markedly reduced in A375 cells. These findings not only reflected differences between melanoma cell lines in basal expression of NF-κB-regulated genes, but also suggested other parthenolide targets involved in cell cycle progression, migration, invasiveness and survival.

Conclusions:

Inhibition of constitutive and therapeutically induced NF-κB pathway by parthenolide might be useful in the treatment of melanoma, although the diversity of changes induced in melanoma cells with different genetic backgrounds indicate context-dependent poly-pharmacological properties of this compound.     

Patch test reactivity to feverfew‐containing creams in feverfew‐allergic patients

Background: The Compositae plant feverfew (Tanacetum parthenium) has long been recognized as an important sensitizer in European Compositae‐allergic patients, mainly because of its content of the sesquiterpene lactone parthenolide. Recently, a parthenolide‐depleted feverfew extract with claimed anti‐inflammatory properties has been developed for use in cosmetics. Objective: The aim of the study was to test, on the basis of patch test reactions, whether persons with contact allergy to feverfew could tolerate creams containing this feverfew extract. Patients/Materials/Methods: Seven patients with feverfew contact allergy were patch tested with two creams containing the feverfew extract. Subsequently, the creams were analysed by liquid chromatography with tandem mass spectrometry to detect parthenolide. Results: Four of the patients tested positive to one of the creams; reactivity was associated with simultaneous positive reactions to parthenolide. This cream was analysed about 2 years later, and no parthenolide was detected, probably because of degradation of the compound. Conclusions: Topical products containing parthenolide‐depleted feverfew extracts may elicit positive patch test reactions in feverfew‐sensitive patients. The reactivity may be enhanced by simultaneous testing with parthenolide, but the reactivity is lost over time, probably because of degradation of parthenolide.     

Parthenolide Inhibits Proliferation of Fibroblast-Like Synoviocytes In Vitro

Parthenolide is a bioactive constituent of an aromatic herb Feverfew (Tanacetum parthenium). It has been found that both parthenolide and extract of feverfew have anti-inflammatory and antinociceptive properties. Moreover, they demonstrate antiproliferative activities on different human tumour cells. The massive hyperplasia of synovial fibroblasts is the one of the most striking features of rheumatoid arthritis. It is not known whether this is due to the proliferation of synovial fibroblasts or to defective apoptosis. We investigated the effect of parthenolide on the proliferation of rabbit synoviocytes cell line HIG-82, rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and human skin fibroblasts (HSF) in vitro. Cell proliferation was assessed by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5'-bromo-2'-deoxy-uridine methods. Parthenolide inhibited proliferation of HIG-82 and human RA-FLS. The proliferation of HSF was inhibited less effectively. The antiproliferative potential of parthenolide was demonstrated.