Cytotoxic Effects of Fascaplysin against Small Cell Lung Cancer Cell Lines

Fascaplysin, the natural product of a marine sponge, exhibits anticancer activity against a broad range of tumor cells, presumably through interaction with DNA, and/or as a highly selective cyclin-dependent kinase 4 (CDK4) inhibitor. In this study, cytotoxic activity of fascaplysin against a panel of small cell lung cancer (SCLC) cell lines and putative synergism with chemotherapeutics was investigated. SCLC responds to first-line chemotherapy with platinum-based drugs/etoposide, but relapses early with topotecan remaining as the single approved therapeutic agent. Fascaplysin was found to show high cytotoxicity against SCLC cells and to induce cell cycle arrest in G1/0 at lower and S-phase at higher concentrations, respectively. The compound generated reactive oxygen species (ROS) and induced apoptotic cell death in the chemoresistant NCI-H417 SCLC cell line. Furthermore, fascaplysin revealed marked synergism with the topoisomerase I-directed camptothecin and 10-hydroxy-camptothecin. The Poly(ADP-ribose)-Polymerase 1 (PARP1) inhibitor BYK 204165 antagonized the cytotoxic activity of fascaplysin, pointing to the involvement of DNA repair in response to the anticancer activity of the drug. In conclusion, fascaplysin seems to be suitable for treatment of SCLC, based on high cytotoxic activity through multiple routes of action, affecting topoisomerase I, integrity of DNA and generation of ROS.     

Sepia Ink Oligopeptide Induces Apoptosis in Prostate Cancer Cell Lines via Caspase-3 Activation and Elevation of Bax/Bcl-2 Ratio

Sepia ink oligopeptide (SIO) is a tripeptide extracted from Sepia ink. To test the hypothesis that SIO inhibits prostate cancer by inducing apoptosis, the effects of SIO on the proliferation of three human prostate cancer cell lines were examined using a CCK-8 assay. SIO significantly inhibited the proliferation of DU-145, PC-3 and LNCaP cells in a time- and dose-dependent manner. Flow cytometry studies showed that exposing DU-145, PC-3 and LNCaP cells to 5, 10, or 15 mg/mL SIO for 24 h increased the percentage of the early-stage apoptotic cells from 11.84% to 38.26% (DU-145), 22.76% to 39.96% (PC-3) and 5.05% to 16.11% (LNCaP), respectively. In addition, typical morphologic changes were observed in the cells with acridine orange/ethidium bromide staining. SIO treatment induced strong S and G₂/M phase cell cycle arrest in a dose-dependent manner in DU-145 and LNCaP. In contrast, SIO treatment induced strong Sub G₁ and G₀/G₁ phase cell cycle arrest in a dose-dependent manner in PC-3. SIO exposure for 24 h decreased the expression of the anti-apoptotic protein Bcl-2 and increased the expression of the apoptogenic protein Bax. Moreover, the Bax/Bcl-2expression ratio was increased. Concurrently, the expression of caspase-3 was upregulated. These data support our hypothesis that SIO has anticarcinogenic properties.     

Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines

The aim of this study was to analyze the effect of Okadaic Acid (OA) on the proliferation of gastric and colon epithelial cells, the main target tissues of the toxin. We hypothesized that OA, at sublethal doses, activates multiple signaling pathways, such as Erk and Akt, through the inhibition of PP2A. To demonstrate this, we carried out curves of doses and time response against OA in AGS, MKN-45 and Caco 2 cell lines, and found an increase in the cell proliferation at sublethal doses, at 24 h or 48 h exposure. Indeed, cells can withstand high concentrations of the toxin at 4 h exposure, the time chosen considering the maximum time before total gastric emptying. We have proved that this increased proliferation is due to an overexpression of Cyclin B, a cyclin that promotes the passage from G2 to mitosis. In addition, we have demonstrated that OA induces activation of Akt and Erk in the three cells lines, showing that OA can activate pathways involved in oncogenesis. In conclusion, this study contributes to the knowledge about the possible effects of chronic OA consumption.     

Metabolite Profiling of Rosemary Cell Lines with Antiproliferative Potential against Human HT-29 Colon Cancer Cells

Plant Foods for Human Nutrition - Rosemary (Rosmarinus officinalis) is a culinary and medicinal plant used in food and pharmaceutical industry. The wide range of biological activities is mainly...     

EPS364, a Novel Deep-Sea Bacterial Exopolysaccharide,Inhibits Liver Cancer Cell Growth and Adhesion

The prognosis of liver cancer was inferior among tumors. New medicine treatments are urgently needed. In this study, a novel exopolysaccharide EPS364 was purified from Vibrio alginolyticus 364, which was isolated from a deep-sea cold seep of the South China Sea. Further research showed that EPS364 consisted of mannose, glucosamine, gluconic acid, galactosamine and arabinose with a molar ratio of 5:9:3.4:0.5:0.8. The relative molecular weight of EPS364 was 14.8 kDa. Our results further revealed that EPS364 was a β-linked and phosphorylated polysaccharide. Notably, EPS364 exhibited a significant antitumor activity, with inducing apoptosis, dissipation of the mitochondrial membrane potential (MMP) and generation of reactive oxygen species (ROS) in Huh7.5 liver cancer cells. Proteomic and quantitative real-time PCR analyses indicated that EPS364 inhibited cancer cell growth and adhesion via targeting the FGF19-FGFR4 signaling pathway. These findings suggest that EPS364 is a promising antitumor agent for pharmacotherapy.     

Antiproliferative Activity of Korean Wild Vegetables on Different Human Tumor Cell Lines

This study was conducted to determine the antiproliferative activity of 24 Korean wild vegetables. The methanol extracts of these wild vegetables were used against lung, breast, colon and gastric cancer cells, and the results were assessed by MTT assay. It was found that at the extract concentration of 400 mgL⁻¹ 14 plants exercised antiproliferative activity over 80% against the lung cancer cells, one plant among six—against breast cancer cells, and two plants among six—against colon cancer cells, respectively. Eighteen wild vegetables had the hyperplasia inhibition activity against gastric cancer cells over 23.6% at all extract concentrations, however, only six plants had the antiproliferative activity over 80% in 600 mgL⁻¹. It was found that the extracts from Youngia sonchifolia, Synurus deltoides, Syneilesis palmata, and Cephalonoplos segetum, in concentration of 400 mgL⁻¹ inhibited the hyperplasia of lung cancer cells over 95% and Angelica gigas—both lung and colon cancer cells over 95%. In conclusion, the studied wild vegetables’ methanol extracts possess dose dependent antiproliferative properties, based on their bioactive compounds, mainly polyphenols, but some of them as Hypericum ascyron against lung cancer are not effective and even course harm.     

Production and Characterization of Antioxidant Properties of Exopolysaccharide(s) from Peanibacillus mucilaginosus TKU032

Natural polysaccharides have received much attention due to their wide range of applications. Although most microbial exopolysaccharides (EPSs) use sugars as the major carbon source, such as glucose or sucrose, in this study, EPSs were induced from a squid pen powder (SPP)-containing medium by Paenibacillus mucilaginosus TKU032, a bacterial strain isolated from Taiwanese soil. Under the optimal culture conditions, the maximum EPS yield (14.8 g/L) was obtained. MALDI-TOF MS analysis of an EPS fraction purified by gel filtration revealed two mass peaks with molecular weights of ∼1.05 × 10⁴ and ∼1.35 × 10⁴ Da, respectively. The analysis of the hydrolysates of TKU032 EPS with cellulase, pectinase or α-amylase indicated that the glycosidic bond of TKU032 EPS is most likely an α-1,4 glycosidic bond and the hydrolysates are similar to those of starch. In addition, the purified EPS demonstrated strong antioxidant abilities.     

几个新选玉米自交系的配合力分析

以张掖市农科所自育的9个自交系按照GriffingD4模型双列杂交,从产量上进行了一般配合力和特殊配合力效应的分析。得出:①9个自交系之间,在一般配合力和特殊配合力方面存在明显差异;②以Z801的一般配合力效应值最高为0.69,Z910次之为0.55,Z936居第3为0.27;③特殊配合力效应较高的组合有Z866×Z911、Z851×Z936、Z853×Z895和Z801×Z936共4个,其效应值超过0.70;④以Z866的特殊配合力方差最大值为0.68,Z936次之为0.60,Z895居第3为0.49;⑤Z936不仅有较高的一般配合力,而且还有较大的特殊配合力方差,将是一个很理想的自交系。     

几个玉米骨干自交系主要性状的配合力分析

8个骨干自交系按griffing双列杂交4设计,配成28个单交组合。采用完全随机区组设计进行试验,分析了生育期、株高、穗位高、穗长、穗粗、穗行数、行粒数、出籽率、千粒重、单株粒重、小区产量等11个农艺性状的一般配合力(GCA)、特殊配合力(SCA)和遗传变量。结果表明,除生育期的SCA外,其余各性状的GCA和SCA都有显著或极显著差异。自交系8112、(素₁×吉840)₂₂₂₂、云1-7、M丹1512的多数性状GCA较好,SCA表现较好的有8112×M丹1522、云1-7×M丹1522、云1-7×M丹1512、云143×M丹1512等组合。表现好的组合符合温带种质×热导系、地方选系×热导系的杂优模式。     

Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1). Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data) and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.     

Purified Brominated Indole Derivatives from Dicathais orbita Induce Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cell Lines

Dicathais orbita is a large Australian marine gastropod known to produce bioactive compounds with anticancer properties. In this research, we used bioassay guided fractionation from the egg mass extract of D. orbita using flash column chromatography and identified fractions containing tyrindoleninone and 6-bromoisatin as the most active against colon cancer cells HT29 and Caco-2. Liquid chromatography coupled with mass spectrometry (LCMS) and ¹H NMR were used to characterize the purity and chemical composition of the isolated compounds. An MTT assay was used to determine effects on cell viability. Necrosis and apoptosis induction using caspase/LDH assay and flow cytometry (PI/Annexin-V) and cell cycle analysis were also investigated. Our results show that semi-purified 6-bromoisatin had the highest anti-cancer activity by inhibiting cell viability (IC₅₀ = ~100 µM) and increasing caspase 3/7 activity in both of the cell lines at low concentration. The fraction containing 6-bromoisatin induced 77.6% apoptosis and arrested 25.7% of the cells in G2/M phase of cell cycle in HT29 cells. Tyrindoleninone was less potent but significantly decreased the viability of HT29 cells at IC₅₀ = 390 µM and induced apoptosis at 195 µM by increasing caspase 3/7 activity in these cells. This research will facilitate the development of these molluscan natural products as novel complementary medicines for colorectal cancer.     

玉米黄改骨干系植株性状的利用潜力评价

利用NCII设计,对玉米生产上常用的5个骨干黄改系的株型性状进行配合力及遗传参数分析。结果表明,株高与雄穗长呈极显著正相关,与雄穗分枝数呈极显著负相关;雄穗分枝数与雄穗长、穗位高和棒三叶夹角呈极显著负相关。雄穗长、雄穗分枝数和穗位高的遗传力较高,适宜在早代选择;株高和棒三叶夹角的遗传力较低,适宜在高代进行选择。黄改系lx9801的株高和雄穗长一般配合力高,特殊配合力方差大,在杂交组合的株高和雄穗长选配中具有重要的利用价值;浚926和浚928的利用应注意改良其穗位偏高的缺点。自交系昌7-2在株高上的特殊配合力和总配合力效应都较好,雄穗分枝数多,适合作父本;自交系K17的株高特殊配合力方差大,穗位高的总配合力效应小,在降低穗位高方面具有较大的利用潜力。     

1BL/1RS易位系HMW-GS组成与品质分析

为深入挖掘1BL/1RS易位系的品质育种潜力,对收集的300份1BL/1RS易位系的高分子量麦谷蛋白亚基(HMW-GS)组成及其品质性状进行了分析。在300份1BL/1RS易位系 Glu-1位点上共检出12种HMW-GS类型和27种HMW-GS组合,表明这些1BL/1RS易位系具有较高的遗传多样性。在 Glu-A1位点上,亚基Null和1亚基的出现频率分别为47.67%和52.33%; Glu-B1位点有7种等位变异,其中出现频率最高的为7+9亚基对(58.67%); Glu-D1位点有3种等位变异, 2+12亚基对为主要类型,出现频率为71.33%。亚基组合类型中,"Null/7+9/2+12"的出现频率最高(31. 67%)。 Glu-A1、 Glu-B1和 Glu-D1编码优质HMW-GS的比例分别为52.33%、38.34%和16.00%,其中31份1BL/1RS易位系在3个位点均编码优质HMW-GS类型。300份1BL/1RS易位系的品质变异范围较大,有9份材料具有较高的品质育种价值。     

Cytotoxic Effect of Natural trans-Resveratrol Obtained from Elicited Vitis vinifera Cell Cultures on Three Cancer Cell Lines

trans-Resveratrol (trans-R) has been reported to be a potential cancer chemopreventive agent. Although its cytotoxic activity against different cancer cell lines has been tested, its effect on human acute leukemia cell lines has scarcely been investigated, and only a few in vitro studies were performed using human breast epithelial cell lines. Due to its potential value for human health, demand for trans-R has rapidly increased, and new biotechnological strategies to obtain it from natural edible sources have been developed. Thus, grapevine cell cultures represent a reliable system of trans-R production since they biosynthesize trans-R constitutively or in response to elicitation. In addition, there are no studies deepen on the inhibitory effect of trans-R, produced by elicited grapevine cell cultures, on growth of human tumor cell lines. In this work, the effect of trans-R extracted from the culture medium, after elicitation of grapevine cell cultures, was tested on two human acute lymphocytic and monocytic leukemia cell lines, and one human breast cancer cell line. The effect of trans-R on cell proliferation was not only dose- and time-dependent but also cell type-dependent, as seen from the different degrees of susceptibility of cancer cell lines tested. As regards the effect of trans-R on cell cycle distribution, low trans-R concentrations increased cells in the S phase whereas a high trans-R concentration increased G₀/G₁ phase in all cell lines. Perturbation of the cell cycle at low trans-R concentrations did not correlate with the induction of cell death, whereas a high trans-R concentration, cell proliferation decreased as a result of increasing apoptosis in the three cell lines. In leukemia cells, trans-R up-regulated the expression of caspase-3 while trans-R-induced apoptosis in breast cells occur through a caspase-3-independent mechanism mediated by a down-regulation of Bcl-2.     

EGCG对细胞的促氧化作用研究进展

EGCG是茶叶中主要的儿茶素类物质,具有多种生物活性。近年来,EGCG促氧化作用得到了广泛关注。本文对国内外细胞实验中EGCG的促氧化作用进行综述。EGCG在细胞培养基中发生自动氧化可以形成细胞外氧化应激环境,这种自动氧化受到培养基种类、EGCG浓度与处理时间、血清含量及p H值等因素影响。在细胞内,EGCG直接提高细胞内活性氧(Reactive Oxidative Species,ROS)和线粒体ROS,或者通过Fenton反应间接产生OH-。EGCG可以影响细胞内转录因子、信号通路与表面生长因子受体的表达与传递,从而影响细胞的一系列生命活动。     

几个优质籼型三系不育系特征特性的观察

通过对新育成的不育系1026A、1032A、1062A、29A与Ⅱ-32A的特征特性进行观察和比较分析,结果表明:1062A柱头外露率低,单株穗粒数多,其他性状与Ⅱ-32A相当;29A性状表现不如Ⅱ-32A;1026A和1032A株叶形态与开花习性等综合性状表现较好,具有较大的应用潜力。     

甜菜单粒种二环系的选育

以引进的甜菜单粒种F_1杂交种为材料,应用套袋自交、镜检、分离等不同选择方法,获得了4个不同倍数性的甜菜二环系及一批有价值的优良二倍体单粒种雄性不育系。目前,以TD401为母本、以多粒种为父本配制的较优组合,已参加了黑龙江省区域化试验。不同来源的二环系,其经济性状、抗褐斑病性表现及育种利用效果不同。