A lactose-binding lectin from the marine sponge Cinachyrella apion (Cal) induces cell death in human cervical adenocarcinoma cells

Cancer represents a set of more than 100 diseases, including malignant tumors from different locations. Strategies inducing differentiation have had limited success in the treatment of established cancers. Marine sponges are a biological reservoir of bioactive molecules, especially lectins. Several animal and plant lectins were purified with antitumor activity, mitogenic, anti-inflammatory and antiviral, but there are few reports in the literature describing the mechanism of action of lectins purified from marine sponges to induce apoptosis in human tumor cells. In this work, a lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated with respect to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death in tumor cells. The antiproliferative activity of CaL was tested against HeLa, PC3 and 3T3 cell lines, with highest growth inhibition for HeLa, reducing cell growth at a dose dependent manner (0.5-10 μg/mL). Hemolytic activity and toxicity against peripheral blood cells were tested using the concentration of IC(50) (10 μg/mL) for both trials and twice the IC(50) for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death caused by CaL in HeLa cells, we performed flow cytometry and western blotting. Results showed that lectin probably induces cell death by apoptosis activation by pro-apoptotic protein Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase and acting as both dependent and/or independent of caspases pathway. These results indicate the potential of CaL in studies of medicine for treating cancer.     

Studies on the synthesis of derivatives of marine-derived bostrycin and their structure-activity relationship against tumor cells

A series of new derivatives (5-29) of marine-derived bostrycin (1) were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds 7, 8, 22, 23, 25, 28 and 29 of the total showed comparable activity to epirubicin, the positive control, against the tested cancer cell lines. However, these compounds also exhibited cytotoxicity towards MCF-10A cells. The structure-activity relationship (SAR) of bostrycin derivatives was also discussed based on the obtained experimental data.     

Antitumor and Antimicrobial Activity of Some Cyclic Tetrapeptides and Tripeptides Derived from Marine Bacteria

Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu) was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu). Cyclic tetrapeptides (CtetPs) were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60–120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80–108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP) scaffold, cyclo(Gly-l-Ser-l-Pro), cyclo(Ser-l-Pro-l-Glu) and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures.     

重组腺病毒Ad－HP对肝癌细胞及肝癌肺转移模型的抑制效应

为探讨重组腺病毒Ad－HP对人肝癌细胞BEL－7402的影响及其对鼠肝癌肺转移模型的抑制作用,本研究利用MTT染色法进行了Ad－HP的体外抑瘤研究,并应用AnnexinV检测、Caspase活性检测、AO／EB染色和DAPI染色等方法分析了Ad－HP的抑瘤方式。另外,本研究利用鼠肝癌细胞H22,建立了肝癌肺转移动物模型,并检测了Ad－HP对肝癌肺转移的抑制作用及其对模型动物免疫的影响。结果表明,Ad－HP能够有效抑制BEL－7402细胞的生长,且其作用具有一定时效和剂效关系趋势;Ad－HP感染导致BEL7402细胞呈现磷脂膜外翻、细胞核皱缩、细胞膜通透性增加和Caspase酶活性增强等典型凋亡特征;应用Ad－HP治疗肿瘤模型能够有效延长模型动物平均生存期,控制转移灶形成,增强NK和CTL活性,上调Thl类细胞因子水平。总之,Ad－HT能够通过诱导细胞凋亡抑制BEL－7402肿瘤细胞增殖,并且能够有效控制肝癌肺转移灶形成,延长模型动物平均生存期。     

紫杉醇抗肿瘤机理与毒副作用

文章综合叙述了紫杉醇的抗肿瘤机理和它的毒副作用。紫杉醇的抗癌机理主要是通过抑制微管解聚使肿瘤细胞有丝分裂终止促进肿瘤细胞凋亡,最后导致肿瘤细胞死亡;紫杉醇体内免疫调节功能也可以对肿瘤细胞起杀伤或抑制作用。另外,对紫杉醇的一般毒性、生殖毒性、遗传毒性进行了介绍。     

姜黄酮骨架双螺环吡咯氧化吲哚类化合物的合成及其抗白血病活性研究

本文以各种取代的靛红1、二烯酮3-烯基氧化吲哚2与脯氨酸或硫代脯氨酸,在有机溶剂乙腈中回流,进行1,3-偶极子3+2环加成反应,获得6个新型的姜黄酮骨架双螺环吡咯氧化吲哚类化合物(3a~3f,Scheme 1),产率65~81%,dr值10∶1~15∶1,其结构经~1H NMR,~(13)C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了3a~3f对人白血病细胞(K562)的体外抗肿瘤活性。结果表明:化合物3a对K562具有一定的抑制活性(IC50为27.9μM),接近于阳性对照药顺铂。     

桢楠精油、精气化学成分及精油生物活性研究

【目的】研究楠木(Phoebe zhennan)(桢楠)精油、精气的化学成分及其生物活性,为楠木养生价值的开发利用提供参考。【方法】以四川桢楠为材料,通过水蒸气法提取桢楠精油,使用气相色谱质谱联用仪分析桢楠精油、精气的化学成分;以白血病HL-60株、肺癌A-549细胞株、肝癌SMMC-7721细胞株、乳腺癌MCF-7细胞株和结肠癌SW480细胞株等5种癌细胞株和大肠杆菌(ATCC25922)、金黄色葡萄球菌(ATCC29213)、肠沙门氏菌(ATCC14028)、铜绿假单胞菌(ATCC27853)等4种细菌为待测对象,评价桢楠精油的抗肿瘤和抑菌活性。【结果】桢楠精油主要成分为沉香螺旋醇,其相对含量为28.26%;其次为愈创木醇,其相对含量为21.84%;第三是γ-桉叶醇,其含量为8.98%。精气主要成分为沉香螺旋醇,其相对含量为11.93%;其次为α-姜黄烯和愈创木醇,其相对含量分别为7.08%和6.67%。桢楠精油对白血病HL-60细胞株、肺癌A-549细胞株等5种癌细胞有较好的抑制作用,IC50均在50μg/mL以内;同时,桢楠精油对供试的革兰氏阴性菌和阳性菌均具有抑制作用。【结论】桢楠精油、精气成分有一定相似性,但精气成分更加复杂;桢楠精油对5种癌细胞株有显著抑制作用,但对4种受试细菌的抑菌效果差异较大,且抑菌效果不明显。     

姬松茸多糖抗肿瘤的实验研究

应用细胞培养技术 ,观察了姬松茸多糖对K5 6 2和HL - 6 0细胞系的影响。研究结果表明 ,实验组活细胞数、集落形成明显减少 ,荧光显微镜下所见凋亡细胞显著增加。提示姬松茸多糖具有抗肿瘤效果。为了探讨姬松茸多糖抗肿瘤的机理 ,本实验还应用反义寡聚脱氧核糖核酸技术 ,进一步观察了姬松茸多糖与人端粒酶反义核酸协同诱导HL - 6 0细胞系凋亡的作用 ,实验结果表明 ,姬松茸多糖与反义寡核苷酸联合使用 ,可促进HL- 6 0细胞凋亡。     

肿瘤多肽疫苗的研究进展

肿瘤的发生、发展和治疗与机体免疫系统功能密切相关,伴随着肿瘤抗原、抗原呈递、T 细胞识别机制的突破性研究进展,研究者发现抗肿瘤多肽疫苗能够通过肿瘤抗原多肽识别抗原呈递细胞（antigen presenting cell ,APC）表面的主要组织相容性复合体（major histocompatibility complex ,M HC）分子,形成肽‐M HC‐T细胞受体（T cell receptor ,TCR）复合物,引起相应的细胞毒性 T 淋巴细胞（cytotoxic T lym‐phocyte ,CTL）免疫反应,从而杀伤肿瘤。因此,研制既能打破肿瘤患者存在的免疫耐受又能诱发针对肿瘤相关抗原（tumor‐associated antigen ,TAAs）特异性免疫应答的高效多肽疫苗已成为肿瘤免疫治疗研究的热点。文章综述了肿瘤多肽疫苗抗肿瘤相关机制及其在该领域所取得的最新临床研究进展。     

人参皂苷代谢产物M1及其脂肪酸酯EMl抗肿瘤活性研究进展

目的:介绍人参皂苷代谢产物20—O—β—D—吡喃葡萄糖—20(S)—原人参二醇皂苷(M1)及其脂肪酸酯(EM1)抗肿瘤活性和EMl合成的研究进展,为其深入研究提供参考。方法:对近年来有代表性的文献进行分析、归纳。结果:人参皂苷代谢产物及其脂肪酸酯有抗肿瘤活性。结论:EM1抑制肿瘤作用比M1强,EM1可能是人参皂苷在体内的真正的活性形式。EM1的药代动力学和生理学需进一步深入研究。