Antitumor activity of polysaccharides isolated from Patrinia heterophylla

The research investigated the effect of Patrinia heterophylla Bunge (Valerianaceae) polysaccharides (PHB-P1) on U14-bearing mice. The tumor weight of mice treated with PHB-P1 (30, 60?mg/kg body weight) was significantly lower than that of the control group, a decrease of serum lactate dehydrogenase (LDH) activity was observed, and the serum alkaline phosphatase (AKP) level was increased slightly. The number of apoptotic tumor cells was significantly increased in the mice by treatment of PHB-P1 (30, 60?mg/kgbw). Cell cycle analysis showed the accumulation of tumor cells in the G2/M phase and a relative decrease of the S phase. By the immunohistochemical analysis, PHB-P1 (30, 60?mg/kgbw) might up-regulate the expression of p53 and Bax, and significantly inhibited the expression of Bcl-2 in tumor tissues. In conclusion, PHB-P1 could inhibit tumor growth and induce tumor cell apoptosis.     

Antitumor activity of the Korean Mistletoe Lectin is attributed to activation of macrophages and NK cells

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 microg/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26-M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity, i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.     

钩吻生物碱化合物抗肿瘤效应及其诱导凋亡作用

目的研究钩吻生物碱化合物抗肿瘤效应及其诱导凋亡作用。方法①在小鼠H22肝癌细胞小鼠移植性肿瘤模型上观察钩吻生物碱化合物对H22小鼠实体瘤的抑制作用;②AO／EB荧光染色法观察凋亡细胞的形态学变化;流式细胞仪PI染色检测细胞周期变化及凋亡率。结果腹腔注射钩吻素子对H22小鼠实体瘤的抑瘤率为40．29％、36．57％、22．89％;钩吻素甲对小鼠H22实体瘤的生长具有一定的抑制作用,抑瘤率为28．91％、16．85％、9．68％;但1-甲氧基钩吻碱小鼠H22实体瘤没有明显的抑制作用。钩吻素子可诱导SW480细胞发生凋亡形态学改变．并且可使SW480细胞周期阻滞于s期,阻止细胞从s期至G2期转移,从而诱导其凋亡。结论钩吻生物碱化合物特别是钩吻素子具有较强的抗肿瘤活性并具有一定的构效关系,钩吻索子的抗肿瘤作用机制可能与阻滞肿瘤细胞周期和促进肿瘤细胞凋亡作用有关。     

Antitumor Activity of Extracts from Peperomia elongata.

Abstract

The cytotoxic potential of ethanol extracts from Peperomia elongata. H. B. & K. (Piperaceae) were evaluated against human cancer cell lines by the MTT method. The samples considered cytotoxic were tested for antimitotic activity with the sea urchin egg development test and for hemolytic activity using mice erythrocytes. The extracts from leaves (hexane), stems (ethanol, hexane, hexane:AcOEt, AcOEt, and MeOH:H₂O insoluble), and roots (R4) presented potential cytotoxic action. The stems extracts showed the highest toxicity in all tumor cell lines tested, with an IC₅₀ ≤ 9.0 µg/mL for ethanol extract, IC₅₀ ≤ 11.6 µg/mL for MeOH:H₂O insoluble, IC₅₀ ≤ 7.3 µg/mL for hexane extract, IC₅₀ ≤ 11.4 µg/mL for hexane: AcOEt, and IC₅₀ ≤ 16.2 µg/mL for AcOEt extract. All extracts considered cytotoxic for tumoral cell lines presented antimitotic activity. The samples from roots (R4) and stems (ethanol, MeOH:H₂O insoluble, and hexane extract from leaves) were found to possess lytic activity in mice erythrocytes but in higher doses (> 125 µg/mL). Further studies for the isolation and identification of the active principles of these extracts should be undertaken.     

Inhibitory effects ofBifidobacterium Spp. isolated from a healthy korean on harmful enzymes of human intestinal microflora

Five hundreds of bifidobacteria were isolated from a healthy Korean and the inhibitory effects of these isloated bacteria on harmful enzymes of human intestinal microflora were examined by cocultivation of the isolated bifidobacteria withE. coli or total human intestinal microflora. In comparison with the results ofE. coli or intestinal microflora cultivation,Bifidobacterium breve K-110,B. breve K-111 andB. infantis K-525 effectively inhibited harmful enzymes (β-glucuronidase and tryptophanase) of f.coli and lowered the pH of the culture media. Also they inhibited the harmful enzymes (β-glucosidase, β-glucuronidase, tryptophanase and urease) and ammonia production of intestinal microflora, and lowered pH of the culture media by increasing lactic acid bacteria of intestinal microflora. When these isolated bifidobacteria were administered on mice, fecal harmful enzymes were also inhibited. Among tested bifidobacteria,B. breve K-110 had the highest inhibitory effect of fecal harmful enzymes.     

海洋放线菌11014中抗肿瘤活性成分的研究Ⅰ.环二肽

为研究具有抗肿瘤活性的海洋放线菌11014发酵物中的活性成分，采用活性追踪的方法．经溶剂萃取、硅胶柱层析及制备HPLC等分离得到13个环二肽，通过理化性质及波谱学分析，分别确定为环（亮氨酸-丙氨酸）．环（亮氨酸-甘氨酸），环（异亮氨酸-丙氮酸），环（缬氮酸-丙氮酸）．环（丙氨酸-苯丙氮酸），环（苯丙氮酸-甘氮酸）．环（酪氮酸-甘氮酸），环（脯氮酸-酪氮酸），环（脯氨酸-苯丙氨酸），环（4-羟基-脯氮酸-苯丙氮酸）．环（4-羟基-脯氮酸-亮氨酸）．环（脯氮酸-缬氨酸），环（脯氮酸-亮氨酸）。首次以磺酰罗丹明法对这些化合物的抗肿瘤活性进行了测试，化合物环（4-羟基-脯氨酸-苯丙氨酸）具有较明显的抗肿瘤活性（5μg／ml浓度抑制率为48．3％）。     

烯二炔类大分子抗肿瘤抗生素C1027抗菌与抗肿瘤活性差异的研究

Ｃ１０２７具有极强杀伤肿瘤细胞活性,作用靶点在ＤＮＡ,但Ｃ１０２７ 的抗菌活性不强,如能了解差别出现的原因,就可进一步掌握Ｃ１０２７的抗菌作用机制,并为将来在临床上确定其应用范围打下良好基础。对Ｃ１０２７ 的抗肿瘤活性与抗菌活性的差异的初步研究结论如下：大分子Ｃ１０２７ 与小分子博莱霉素Ａ５ 相比,对肿瘤细胞抑制作用明显高于后者;对细菌的抑制作用却明显低于博莱霉素Ａ５;对支原体的抑制作用略大于博莱霉素Ａ５ 。Ｃ１０２７（１００～０．０１ｍ ｇ／Ｌ）对大肠埃希氏菌Ｂ原生质体ＤＮＡ合成几乎无抑制作用,同对大肠埃希氏菌Ｂ菌体的ＤＮＡ合成抑制作用相比,差别不大。细胞壁并非阻碍Ｃ１０２７损伤大肠埃希氏菌ＢＤＮＡ的主要因素。     

Antitumor and antioxidant activity of protocatechualdehyde produced from Streptomyces lincolnensis M-20

We characterized the biological functions of protocatechualdehyde (PA) isolated from the butanol extract of culture supernatant from Streptomyces lincolnensis M-20. Following butanol extraction, it was purified by silica gel and Sephadex LH-20 column chromatography. PA was analyzed by Furier Transform Infrared Spectroscopy (FT-IR), Gas chromatograph-Mass Spectrometer (GC-MS), and Nuclear Magnetic Resonance (NMR). PA had potent antioxidant activity, as measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Antitumor activity against MCF-7 human breast cancer cells was evaluated by the 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium-bromide (MTT) assay. PA treatment (0∼150 μM) dose-dependently blocked apoptosis, as shown by improved cell viability and inter-nucleosomal DNA fragmentation. Our findings suggest that Streptomyces lincolnensis M-20, a lincomycin producer, also produces protocatechualdehyde.     

褶纹冠蚌Cristaria plicata提取物抗肿瘤作用的实验研究

从褶纹冠蚌中提取亲水性物质(Ⅰ组分)，采用超滤法将Ⅰ组分分级为相对分子质量≤30kD的多糖(Ⅱ组分)和相对分子质量≥30kD糖蛋白（Ⅲ组分)两部分。研究结果表明Ⅲ组分对小鼠L1210淋巴白血病癌细胞、S180肉瘤、EAC腹水瘤显示出一定的杭肿癌活性，同时对荷瘤小鼠NK细胞杀伤活性有明显的增强作用，而Ⅱ组分则无抗肿瘤作用，但对荷瘤小鼠NK细胞杀伤活性有一定的增强作用。     

一氧化氮供体型非甾体抗炎药抗肿瘤作用机制研究现状

概述一氧化氮供体型非甾体抗炎药（NO—NSAIDs）抗肿瘤药理学实验研究，着重综述该类药物抗肿瘤作用机制研究进展。在NO-NSAIDs中，NO-阿司匹林被研究得最为深入，其有多种作用机制，包括阻断Wnt信号通路、抑制NF-κB的激活、抑制一氧化氮合酶、调控环氧合酶-2、调节Keapl-Nrf2和MAPK信号通路等，这些机制可能在该类药物的抗癌作用中扮演着不同角色。     

微生物来源的作用于细胞信号传导及细胞周期的抗肿瘤化合物

综述近几年在微生物中发现的对细胞信号传导及细胞周期有干扰作用的具有抗肿瘤活性的化合物。简单介绍了这些化合物的来源、结构及生物活性。     

海绵共附生放线菌Saccharopolyspora sp.nov中抗肿瘤活性成分的研究

羽毛山海绵（Mycale plumose）来源的糖多孢菌（Saccharopolyspora sp.nov SP2-10）具有诱导肿瘤细胞坏死的活性。本文对其发酵产物的活性部位乙酸乙酯层进行活性追踪分离．共得到7个化合物；利用理化性质和波谱学方法鉴定它们的结构分别为胆甾醇、邻苯二甲酸二异丁酯、4（2，4-二羟基苯甲酰氨基）苯甲酸、苯丙胺酸、脱氧鸟苷、鸟苷和N-乙酰酪胺I并初步评价上述化合物的抗肿瘤活性，结果表明，邻苯二甲酸二异丁酯显示强细胞毒活性。     

Antitumor activity and toxicity relationship of annonaceous acetogenins

Annonaceous acetogenins (ACGs) are one of the most interesting classes of natural products appearing in the past two decades. Here, we studied the antitumor activity and toxicity relationship of ACGs including annosquamin B (1), bullatacin (2) and annosquatin B (3) in vivo. A single intraperitoneal (i.p.) injection of 100 μg/kg of annosquamin B, bullatacin and annosquatin B did not cause side effects in normal mice. Bullatacin treatment with five doses of 25 and 50 μg/kg in H₂₂ hepatoma cells bearing mice resulted in about 61% reduction in tumor growth with hematologic parameters increased significantly in normal mice. Annosquamin B and annosquatin B treatments with 10 doses of 25, 50 and 100 μg/kg in the H₂₂ hepatoma cells transplantation tumor model mice resulted in maximum 53.7% and 58.7% reduction in tumor growth, respectively, and did not cause severe side effects in normal mice. This study provided the evidence that adjacent bis-THF ACGs showed higher antitumor activity and toxicity than mono-THF and nonadjacent bis-THF ACGs in vivo. Furthermore, it was found that bullatacin led to liver and kidney toxicity via increasing calcium concentration, ROS production, and Bax expression and Bax/Bcl-2 ratio in rats with repeated treatment with bullatacin for 3 weeks.     

Antitumor constituents from Alternanthera philoxeroides

Two new compounds, alternanthin B (1) and N-trans-feruloyl-3,5-dimethoxytyramine (2), along with four known compounds (3-6) were isolated from the aerial parts of Alternanthera philoxeroides. Their structures were elucidated on the basis of spectroscopic methods. The antitumor activity of the isolated compounds was also evaluated.     

Design and Synthesis of a Gossypol Derivative with Improved Antitumor Activities

A novel chemical process has been devised for the synthesis of a new derivative of gossypol, 6,7,6′,7′‐tetrahydroxy‐5,5′‐diisopropyl‐3,3′‐dimethyl‐[2,2']binaphthalenyl‐1,4,1′,4′‐tetraone (Apogossypolone). This new process has only four steps, with a shorter synthesis span, a simple purification process, and improved yield and quality. The structure of apogossypolone was characterized by ¹H‐nuclear magnetic resonance, ¹³C‐nuclear magnetic resonance, mass spectroscopy, infrared spectroscopy, and elemental analysis. Cell‐cytotoxicity assay demonstrates that apogossypolone is three‐ to six‐fold more potent than the parent compound, (–)‐gossypol, in inhibiting the human prostate tumor cell lines PC‐3 and DU‐145 as well as the human breast cancer cell line MDA‐MB‐231. The colony‐formation assay with DU‐145 cells showed that apogossypolone inhibited more than 70% of colony formation at 1 μM, whereas (–)‐gossypol at 10 μM only inhibited less than 50% of colony formation. The results indicate that apogossypolone exerts strong antitumor activities in human prostate and breast cancer cells, and thus represents a promising cancer therapeutic.     

Antitumor activity of flavones isolated from Artemisia argyi

The flavones 5,6-dihydroxy-7,3',4'-trimethoxyflavone ( 1), 5,6,4'-trihydroxy-7,3'-dimethoxyflavone ( 2), 5-hydroxy-3',4',6,7-tetramethoxyflavone, 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone, ladanein, and hispidulin were isolated from the methanolic extracts of the aerial parts of Artemisia argyi and structures of the compounds were elucidated on the basis of their spectral data. These flavones inhibited farnesyl protein transferase with IC 50 values of 25 - 200 microg/mL. Compound 2 inhibited proliferation of a couple of tumor cell lines and also inhibited neovascularization in a chick chorioallantoic membrane assay. Without loss of body weight of nude mice, compounds 1 and 2 inhibited growth of a colon tumor (SW620) by 44.6 % and 14.6 %, respectively.     

哌啶酮类法尼基转移酶抑制药的微波幅射合成与抗肿瘤活性

目的合成设计哌啶酮类法尼基转移酶抑制药，并对其抗肿瘤活性进行初步评价。方法以取代苯甲醛为起始原料，经Perkin反应和Michael加成，最后在微波辐射条件下环合得到目标化合物，并用MTT法测试它们抑制人Hela细胞和ANC-1细胞的IC50值。结果采用微波辐射技术合成哌啶酮类化合物，反应时间为20～45 min，产率为36.0%～67.1%。经1H-NMR、ESI-MS及IR对化合物的结构确证，总共合成11个新化合物。初步抗肿瘤活性测试结果显示11个目标化合物均有抑瘤活性，其中8个化合物IC50值低于氟尿嘧啶。结论哌啶酮类法尼基转移酶抑制药的合成路线可靠，具有显著抗肿瘤活性。     

诱导细胞凋亡的抗肿瘤抗生素

细胞凋亡是肿瘤防治的一个非常重要的机制，诱导细胞凋亡的抗肿瘤抗生素的面世开辟了肿瘤化疗药物研发的新途径。概述诱导细胞凋亡的抗肿瘤抗生素种类、来源、抗肿瘤谱及实验研究，并对其作用机制进行探讨。     

蒲圻贝母中蒲贝酮碱的抗肿瘤活性

从蒲圻贝母中分得的一种新生物碱蒲贝酮碱，按一定剂量灌胃给药，显示了强的抗小鼠艾氏腹水癌（EAS，实体型），宫颈癌（U14，实体型）及肝癌（HePA,实体型）的活性。     

熊果酸衍生物与查耳酮缀合物的合成及抗肿瘤活性研究

目的 设计、合成喹喔啉熊果酸-查耳酮缀合物.方法 以喹喔啉熊果酸为先导化合物,将查耳酮通过酯化反应拼接到喹喔啉熊果酸得到了一系列喹喔啉熊果酸-查耳酮缀合物,并通过MTT法测试其抗癌活性.结果 合成了6个喹喔啉熊果酸-查耳酮缀合物,其结构均通过1H NMR,13C NMR和HRMS加以确认.初步的生物活性结果表明,这些缀合物对MCF-7、PC-3、GBC-823和KB细胞均有抑制活性,尤其是对MCF-7细胞的抑制活性与熊果酸相比均有提高,其中化合物5(IC50=14.2μmol·L-1),6(IC50=15.3μmol·L-1)和7(IC50=10.6μmol·L-1)对MCF-7细胞的抑制活性甚至强于临床上应用的药物他莫昔芬(IC50=15.9μmol·L-1).同时,这些缀合物对正常的乳腺上皮细胞MCF-10A没有毒性.结论 本研究为开发高效、低毒的的熊果酸衍生物提供了信息和依据.