细胞凋亡诱导剂研究进展

细胞凋亡诱导剂作为癌症治疗药物日益受到重视,并已应用于临床研究,是一类非常有应用前景的药物.综述了近年来细胞凋亡诱导剂的研究状况及进展,重点介绍了它们的结构类型及作用特点.     

一个新的杆状病毒凋亡抑制基因的克隆及鉴定

缺失功能性ｐ３５基因的苜蓿尺蠖核形多角体病毒（ＡｃＮＰＶ）突变体（ｖΔＰ３５Ｋ／ｐｏｌ＋）感染草地夜蛾细胞（Ｓｆ９和Ｓｆ２１）［１］及海灰翅夜蛾细胞（ＳＬ２）［２］时，引起细胞凋亡，从而使病毒的感染流产．我们发现海灰翅夜蛾核形多角体病毒（ＳｌＮＰＶ）...     

Study on Extraction Process of Root of Henry Wood Betony Polysaccharides and Their Antitumor Activity against S180

We optimized the hot water extraction of polysaccharides from the root of Henry wood betony (RHWPs) using a uniform test and explored their anti-tumor activities in vitro and in vivo. The optimal extraction conditions were as follows: 40 min extraction time, liquid/solid ratio 30 mL/g, 100 min soaking time, two extraction cycles, 100% ethanol concentration, and extraction temperature of 80 °C. The molecular weight distribution of RHWPs with MWs was 228,600 g/mol and 5001 g/mol. The IR spectrum further indicated that RHWPs are acidic polysaccharides containing pyranose and furan rings. The main monosaccharides found in RHWPs were mannose, ribose, l-rhamnose monohydrate, glucuronic acid, galacturonic acid, glucose, galactose, xylose, arabinose, and fucose. RHWPs inhibited the proliferation of S180 tumor cells and induced apoptosis in vitro. Oral administration of RHWPs to tumor-bearing mice significantly inhibited the growth of the S180 xenografts, accelerated apoptosis in tumor cells, and expanded the necrotic regions. Furthermore, RHWPs also markedly increased the levels of TNF-α, IFN-γ, and IL-2 in the sera of tumor-bearing mice, and activated immune cells such as lymphocytes, NK cells, and macrophages, thereby inducing tumor cell apoptosis. Taken together, RHWPs are a promising anti-tumor agent that ought to be explored further.     

稀土对人正常肝细胞株7701和人宫颈癌Hela细胞生长的影响及其诱导细胞凋亡的作用

采用MTT法考察了16种稀土元素在9×10-8~2×10-4mol.L-1浓度范围内对体外培养的人正常肝细胞株7701细胞和宫颈癌Hela细胞的生长的影响。结果表明,稀土对细胞生长的影响存在浓度依赖性;低浓度促进细胞增殖,高浓度抑制细胞生长;不同稀土离子对细胞作用强弱不同,稀土间存在轻重分组效应;不同细胞对稀土的响应不同,表现出稀土对正常细胞和癌细胞作用的某种选择性。Hoechst 33258标记细胞DNA,用激光共聚焦显微镜和流式细胞仪对稀土处理的肝细胞株7701进行形态学观察和DNA含量分析。结果表明,较高浓度的稀土作用后的肝细胞株7701出现了明显的凋亡特征,稀土表现出的细胞毒性作用,其本质是诱导细胞发生凋亡。     

Natural products of the medicinal fungus Ganoderma lucidum: occurrence,biological activities,and pharmacological functions

Ganoderma lucidum, a fungus used in traditional Chinese medicine, produces polysaccharides and oxygenated triterpenoids with a very broad spectrum of biological activities and pharmacological functions. Among the Ganoderma triterpenoids, many pairs of C-3 alpha/beta stereoisomers and C-3/C-15 positional isomers have been identified. Biosynthetic study has indicated that the C-3alpha series of oxygenated triterpenoids is derived from the C-3beta series via an oxidation-reduction pathway. The interaction of Ganoderma triterpenoids with human platelets in the induction of aggregation and inhibition of agonist-induced aggregation and signal transduction has been elucidated. Reduction of cellular mevalonate content to a stage in which cholesterol synthesis is strongly inhibited and cell growth is marginally arrested sensitizes hepatoma cells to the oxygenated triterpenoids. A combination treatment of lovastatin and Ganoderma triterpenoids in animal studies has exhibited a potential anticancer effect.     

Synthesis, stereochemistry confirmation and biological activity evaluation of a constituent from Isodon excisus

A synthesis and stereochemistry confirmation of a constituent recently isolated from the whole plant Isodon excisus is reported. An enantioselective catalytic boron-mediated reduction of an α-bromoketone was utilized in the key synthetic transformation. The methodology described herein was also used for the synthesis of the natural product's enantiomer and several derivatives. In addition, the compounds were evaluated for inhibitory activity in a caspase induction assay. The natural product was found to be devoid of activity, but several derivatives had moderate inhibitory activity (EC₅₀<1 μM).     

1-烷（苯）氧基-3-（3，4-亚甲基二氧）苯基-2-丙醇的合成与生物活性研究

黄樟素氧化物与烷氧基钠和苯氧基钠反应，区域选择性地开环加成，生成1-烷 （苯）氧基-3-（3，4-亚甲基二氧）苯基-2-丙醇。该系列化合物具有诱导细胞凋 亡与分化的生物活性。     

Preparation and in vitro investigations of triphenyl[ω‐(tetrahydro‐2H‐pyran‐2‐yloxy)alkyl]tin(IV) compounds

The reaction of SnPh₃Li with X(CH₂)_n O–THP (THP = tetrahydro‐2H ‐pyran‐2‐yl; n  = 3, 4, 6, 8, 11; X = Cl, Br) afforded organotin(IV) compounds with the general formula Ph₃Sn(CH₂)_n O–THP ( 1 – 5 ). The tetraorganotin(IV) compounds were characterized using multinuclear NMR and infrared spectroscopies and high‐resolution mass spectrometry. Anticancer activity of the synthesized compounds was tested in vitro against the A2780 (ovarian), A549 (lung), HeLa (adenocarcinoma) and SW480 (colon) tumour cell lines with SRB assay. The in vitro investigations revealed that when a shorter chain was present a higher activity was achieved; however compounds 1 – 5 were found to be less active than cisplatin. In addition, the most active compound, 1 , enters A2780 cells and causes apoptosis by triggering both intrinsic and extrinsic caspase pathways.     

Structure‐cytotoxicity relationship for apoptotic inducers organotin(IV) derivatives of mandelic acid and L‐proline and their mixed ligand complexes having enhanced cytotoxicity

Structure‐cytotoxicity relationship of di?/tri‐organotin(IV) derivatives of mandelic acid ( 1 – 4 ), L‐proline ( 5 – 7, 15, 16 ), and mixed ligand complexes of latter with 1,10‐phenanthroline ( 8 – 14 ) investigated on the basis of MTT assay against human cancer cell lines, viz. MCF‐7 (mammary cancer), HepG2 (liver cancer) and PC‐3 (prostate cancer) in vitro indicated that all complexes except methyl‐ and octyl‐ analogues displayed potential cytotoxicity. The most active one is dibutyltin(IV) mandelate ( 2 ) exhibiting IC₅₀ 2.03 ± 0.40, 0.98 ± 0.23 and 3.86 ± 1.68 μM against MCF‐7, HepG2 and PC‐3, respectively, which is ≈ 15 and 2.5 times against MCF‐7, 20 and 5 times against HepG2 and 5 and ≈ 3 times against PC‐3 more cytotoxic than cis‐platin and 5‐fluorouracil, respectively. Diorganotin(IV) derivatives of mandelic acid are more cytotoxic than triorganotin analogues. Organotin(IV) derivatives of L‐proline (except Bu₃Sn(Pro) 16 ) are less cytotoxic than those of mandelic acid but their cytotoxicity is enhanced by complexion with 1,10‐phenanthroline. This may be due to the structural planarity and extended π system of 1,10‐phenanthroline which facilitates their transportation across the cell membrane and enhances the possibility of DNA intercalation over the planar L‐proline ring, and eventually, their DNA binding affinity so as to interfere with the cellular functions of DNA leading to apoptosis. Various biophysical experiments such as DNA fragmentation, acridine orange and comet assays, and flow cytometry assay using annexin V–fluorescein isothiocyanate (FITC) and propidium iodide (PI) have been carried out in order to ascertain their mode of action. The observed results indicated that the major cause of cancer cell death is apoptosis, but a minor role played by necrosis cannot be excluded. It is concluded on the basis of the observed results that the nature and number of organic groups bonded to tin as well as the nature of counter anions play an important role in determining the cytotoxicity of organotin(IV) compounds.     

Pharmacological properties of dicyanidoaurate(I)-based complexes: characterization and single crystal X-ray analysis

The synthesis of three bimetallic cyanido complexes with edbea [2,2′-(ethylenedioxy)bis(ethylamine)] ligand is reported. [Ni^II(μ-edbea)₂{Au(μ-CN)₂}₂]_n (1), [{Cu^II(edbea)}₂{Au(μ-CN)₂}₄]_n (2) and [Cd^II(edbea)₂][Au(CN)₂]₂·H₂O (3) were fully characterized by elemental, infrared, XRD (3), ESI-MS and thermal analysis. The DNA/BSA binding properties of these complexes were evaluated by spectrophotometric titration, fluorometric ethidium bromide kinetics, and DNA electrophoresis studies and their partially minor groove binding mode between the base pairs of DNA and electrostatic interaction between the amino acid residues of BSA were explained. The complexes were tested for their pharmacological properties. These molecules had excellent in vitro antiproliferative activity and also exhibited a strong tumor inhibiting effect against HT29, HeLa, C6 and Vero cell lines. These complexes had metastatic features as they are able to reduce cell migration activity and suppress tumor growth in vitro. Analysis of the DNA topoisomerase I relaxing activity indicates that the complexes do not inhibit topoisomerase I which regulates the topological states of the DNA double helix during DNA processing reactions. The TUNEL and DNA laddering assay results indicated that these compounds may destroy cell maintenance by triggering apoptosis. Immunohistochemistry staining analysis demonstrated that these complexes significantly decreased the expression of Bcl-2 in HeLa and HT29 cells while increasing the expression of P53 levels. Overall, the potent antiproliferative activity, low cytotoxic effect, good solubility, and micro molar range dosage observed for these complexes emphasizes their potential as anticancer drug candidates.