澳洲茄碱的抗肿瘤活性及其机制研究进展

澳洲茄碱（SS）是一种天然来源的生物活性小分子化合物,已经被证实具有抗菌、抗炎和抗肿瘤等功效。在抗肿瘤作用方面,SS可以通过多种机制在不同类型肿瘤中有效发挥抗肿瘤作用,其作用机制包括诱导肿瘤细胞凋亡、阻滞肿瘤细胞周期、诱导肿瘤细胞铁死亡、调控肿瘤相关非编码RNA、调节免疫和炎症反应、削弱肿瘤细胞的侵袭和转移能力、抑制糖酵解进程和肿瘤干细胞的产生等,涵盖了肺癌、肝癌、胃癌、乳腺癌、胆管癌、膀胱癌、胰腺癌、白血病、骨肉瘤等多种癌症类型。阐明SS在不同类型肿瘤中的抗肿瘤活性及其作用机制,为促进SS抗肿瘤作用机制的进一步研究和开发更有效安全的抗肿瘤药物提供了重要的理论基础。     

当归化学成分及抗肿瘤作用机制的研究进展

近年来,随着天然药物化学分离和提纯技术水平的不断提高,以及药理学研究的深入,当归抗肿瘤活性成分作用机制的研究取得了较大进展。对当归有效成分进行研究后,发现其具有抗肿瘤、调节免疫、造血、抗血小板聚集、平喘和镇痛等多种作用。当归抗肿瘤作用机制主要包括抑制肿瘤血管生成、影响肿瘤细胞周期、抑制肿瘤细胞生长和增殖、诱导肿瘤细胞凋亡、降低黏附性和侵袭力、抑制肿瘤细胞转移、逆转肿瘤耐药和放化疗增敏等。本文通过对国内外相关文献进行系统梳理和归纳,为明确当归抗肿瘤作用机制和新型抗肿瘤药物的研发提供参考。     

辣椒素预防及抗肿瘤作用机制研究进展

应用天然果蔬中的活性化合物进行预防和治疗肿瘤是目前研究的热点。辣椒素是在辣椒皮质部分中存在的一种生物碱,具有预防和抗肿瘤作用,其抗肿瘤作用机制复杂,主要通过靶向激活辣椒素受体或其他信号通路,引起肿瘤细胞周期停滞、代谢抑制、肿瘤坏死、 凋亡和自噬,抗血管生成和降低癌细胞的转移能力,对多种肿瘤细胞,产生抗肿瘤作用,可作为癌症预防和治疗的潜在药物,特别是与其他抗癌药物联合应用,具有广泛的应用前景。本文就辣椒素预防及抗肿瘤作用机制相关研究进展进行综述。     

诺尼抗肿瘤作用及其机制的研究进展

摘要本文概述了近十多年来国内外有关诺尼抗肿瘤作用及其机制的研究进展,大量试验表明诺尼果汁、果汁提取物、叶子和根提取物均有抗肿瘤作用,可通过诱导肿瘤细胞凋亡、激活宿主免疫系统、抑制血管生成、抗氧化、抑制环氧化酶和阻止致癌物-DNA加合物形成等机制来抑制肿瘤生长。本文希望能为研发以诺尼为原料辅助治疗癌症的药物和食品提供参考。     

Twist 对EMT 调控在循环肿瘤细胞监测与抗癌药物评价中的临床意义*

肿瘤细胞的上皮间质可塑性变化包括上皮- 间质化（epithelial-mesenchymal transition ,EMT ）和间质- 上皮转化（mesenchymal-epithelial transition,MET ）的可逆过程,在循环肿瘤细胞（circulating tumor cells ,CTCs）形成、转归及肿瘤转移过程中起到重要作用。Twist在人横纹肌肉瘤、乳腺癌、胃癌等多种肿瘤中过表达,肿瘤细胞中Twist与多种信号通路连接,形成复杂的网状环路参与调控CTCs中EMT/MET的发生并促进肿瘤细胞向远处转移。因此,通过监测CTCs中Twist本身以及所调控的上皮- 间质表型分子标志物的变化,不仅可以增加肿瘤标志物CTCs的检出率,提供肿瘤临床分期及预后评估的直接证据;而且,对于评估多种抗肿瘤药物的疗效及耐药机制均具有重要的临床意义。      

白藜芦醇的抗肿瘤效应机制

白藜芦醇是一种天然多酚类化合物,具有多种生物学作用,包括神经保护作用、心血管保护作用、抗炎及抗肿瘤作用等.近年来白藜芦醇抗肿瘤作用日益受到关注,其抗肿瘤机制可能是预防肿瘤的发生、延缓肿瘤的发展、促进肿瘤细胞凋亡及抑制肿瘤细胞的侵袭等.     

安罗替尼在晚期恶性肿瘤治疗中的研究进展

安罗替尼是我国自主研发的多靶点小分子酪氨酸激酶抑制剂,具有抗肿瘤血管生成和抑制肿瘤细胞生长的作用,因其具有不良反应小、靶点明确及安全性高等优点,目前已在多种恶性肿瘤中显示出了良好的临床疗效,本文就安罗替尼的抗肿瘤作用机制、其在多种类型肿瘤中的应用以及不良反应与管理等方面的最新研究进展进行综合阐述。     

紫檀芪的抗肿瘤活性研究进展

紫檀芪是白藜芦醇的衍生物之一,对多种肿瘤细胞增殖具有显著抑制作用.其抗肿瘤机制包括诱导肿瘤细胞凋亡、引起细胞周期阻滞及阻断肿瘤细胞生长和增殖信号转导等.紫檀芪有望发展成为新一代的抗肿瘤药物,逐渐受到人们的关注.     

维生素D及其类似物抗肿瘤作用及机制

维生素D及其类似物具有抗肿瘤作用,其机制主要包括诱导肿瘤细胞周期阻滞,促进肿瘤细胞分化,诱使肿瘤细胞凋亡,抑制端粒酶活性,抑制肿瘤转移、侵袭及血管生成以及通过影响生长因子和癌基因来抑制肿瘤等.但是,维生素D及其类似物抗肿瘤作用由多种机制介导,不同通路的精细分子机制仍需深入探讨.维生素D族化合物可能是未来很有希望的抗癌剂.     

MDA 7/IL-24抗肿瘤作用研究进展MDA 7/IL-24抗肿瘤作用研究进展

黑色素瘤分化相关基因(melonoma differentiation associated gene 7,MDA 7)是通过消减杂交法从人黑色素瘤细胞中分离出来的,因其分子生物学特性与IL-10相似,故将其归入IL-10家族,并命名为IL-24。MDA 7/IL-24具有广泛的抗肿瘤生物学作用,它能够通过多种途径对肿瘤细胞产生生长抑制作用,其作用机理与凋亡诱导、细胞自噬、抑制肿瘤新生血管形成和侵袭转移、免疫调节作用等有关。作为一种具有多种途径抗肿瘤作用的细胞因子,MDA 7/IL-24在临床Ⅰ期试验中已显示出良好的治疗效果,被誉为治疗癌症的“魔法子弹”。本文就MDA 7/IL-24在肿瘤治疗中的作用及其机制研究作一综述,以期为MDA 7/IL-24在肿瘤基因治疗中研究提供参考和借鉴。     

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced NF-kappaB activation by tea polyphenols, (-)-epigallocatechin gallate and theaflavins

(-)-Epigallocatechin gallate (EGCG) and theaflavins are believed to be the key active components in tea for the chemoprevention of cancer. However, the molecular mechanisms by which EGCG and theaflavins block carcinogenesis are not clear. In the JB6 mouse epidermal cell line a tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), which causes cell transformation at high frequency, markedly induced NF-kappaB activation. We found that EGCG and theaflavins inhibited TPA-induced NF-kappaB activity in a concentration-dependent manner. These polyphenols blocked TPA-induced phosphorylation of IkappaBalpha at Ser32 in the same concentration range. Moreover, the NF-kappaB sequence-specific DNA-binding activity induced by TPA was also inhibited by these polyphenols. These results suggest that inhibition of NF-kappaB activation is also important in accounting for the anti-tumor promotion effects of EGCG and theaflavins.     

Elimination of Deleterious Effects of Free Radicals in Murine Skin Carcinogenesis byBlack Tea Infusion,Theaflavins & Epigallocatechin Gallate

In recent years, numerous reports have been published on the identification of novel, naturally occurring ‍antioxidants from plants, animals, microbial sources and processed food products. Most natural antioxidants are ‍phenolic compounds, which have a modulatory role on physiological functions and biotransformation reactions ‍involved in the detoxification process, thereby affording protection from cytotoxic, genotoxic and metabolic actions ‍of environmental toxicants. As part of our program on evaluation of food, beverage and traditional medicinal plants ‍for their anticarcinogenic activity, the present report deals with the evaluation of aqueous infusion of Black tea ‍(Camellia sinensis), Black tea extract (80% Theaflavins) & EGCG on mice exposed to the chemical carcinogen ‍DMBA. All the four detoxification enzymes studied viz, GST, GPx, SOD and CAT were found to be activated to ‍different degrees following treatment with black tea and two of its active compounds. The activation of the enzymes ‍was accompanied by significant reduction in lipid peroxidation. The effect on apoptosis and cell proliferation was ‍also studied in mice skin following administration of DMBA. Theaflavins, and EGCG significantly inhibited cell ‍proliferation and induced apoptosis. The observation suggests chemopreventive potential of black tea infusion, ‍black tea extract Theaflavins and the compound EGCG.‍     

Delivery of tea polyphenols to the oral cavity by green tea leaves and black tea extract.

Catechins and theaflavins, polyphenolic compounds derived from tea (Camellia sinensis, fam. Theaceae), have been reported to have a wide range of biological activities including prevention of tooth decay and oral cancer. The present study was undertaken to determine the usefulness of green tea leaves and black tea extract for the delivery of catechins and theaflavins to the oral cavity. After holding either green tea leaves (2 g) or brewed black tea (2 g of black tea leaves in 100 ml) in the mouth for 2-5 min and thoroughly rinsing the mouth, high concentrations of catechins (C(max) = 131.0-2.2 micro M) and theaflavins (C(max) = 1.8-0.6 micro M) were observed in saliva in the 1st hour. Whereas there was significant interindividual variation in the peak levels of catechins and theaflavins, the overall kinetic profile was similar, with t(1/2) = 25-44 min and 49-76 min for catechins and theaflavins, respectively (average coefficient of variation in t(1/2) was 23.4%). In addition to the parent catechin and theaflavin peaks, five unidentified peaks were also observed in saliva after black tea treatment. Hydrolysis of theaflavin gallates, apparently by salivary esterases, was observed in vitro and in vivo. These results indicate that tea leaves can be used as a convenient, slow-release source of catechins and theaflavins and provide information for the possible use of tea in the prevention of oral cancer and dental caries.     

Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)- epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3- fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)- epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.      

Chemoprevention with theaflavins of rat esophageal intraepithelial neoplasia quantitatively monitored by image tile analysis.

The objective of the study was to compare three methods of monitoring the inhibition by dietary theaflavins of N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal intraepithelial neoplasia: the mean tile grade, measured by computer-assisted quantitative image tile analysis; tumor multiplicity; and mean tumor size. A "tile" is defined as a small portion of a microscopic image at x 40, 87 x 292 microm in size. The computer divided the image of esophageal intraepithelial neoplasia into a grid of contiguous tiles and measured four tissue features within each tile based on cytonuclear and tissue architectural changes used by pathologists to diagnose intraepithelial neoplasia. The tile grade is defined as the weighted sum of the four feature measurements within a tile, the weights being determined by Fisher linear discriminant analysis. The mean tile grade of 300 tiles is used to grade rat esophageal intraepithelial neoplasia. NMBA was given s.c., 0.5 mg/kg, three times a week for 5 weeks. Theaflavins were given in the drinking water at 360 ppm (low dose) and 1200 ppm (high dose) throughout the experiment. In a given set of four groups of rats, one group received theaflavins alone, one NMBA alone, one NMBA plus low-dose theaflavins, and one NMBA plus high-dose theaflavins. One set of four groups, four rats/group, was sacrificed at the 15th week and another at the 20th week after starting NMBA; a final set with 15 rats/group was sacrificed at 25 weeks. At the 15th and 20th weeks, the mean tumor grade was the only variable that responded significantly (P < 0.01) to the low dose of dietary theaflavins. In fact, tumor multiplicity and mean tumor size sometimes showed enhancement at these doses. At the 25th week, when there were 15 instead of 4 rats/group, the mean tile grade, tumor multiplicity, and mean tumor size were all significantly (P < 0.01) decreased by both low and high doses of theaflavins. The mean tile grade is a more sensitive and reproducible variable than tumor multiplicity and mean tumor size in detecting the chemopreventive effects of theaflavins on intraepithelial neoplasia in the rat esophagus. This suggests that the mean tile grade may be a useful intermediate end point for use in human chemoprevention trials.     

Comparative chemopreventive mechanisms of green tea, black tea and selected polyphenol extracts measured by in vitro bioassays

Black tea extracts (hot aqueous, polyphenols and theaflavins) and green tea extracts (hot aqueous, polyphenols, epicatechin, epicatechin gallate, epigallocatechin and epigallocatechin gallate) were tested in nine standardized cell culture assays for comparative cancer chemopreventive properties. Most black and green tea extracts strongly inhibited neoplastic transformation in mouse mammary organ cultures, rat tracheal epithelial cells and human lung tumor epithelial cells. Nearly all tea fractions strongly inhibited benzo[a]pyrene adduct formation with human DNA. Induction of phase II enzymes, glutathione-S-transferase and quinone reductase, were enhanced by nearly all tea fractions, while glutathione was induced by only a few fractions. Ornithine decarboxylase activity was inhibited by nearly all the green tea fractions, but none of the black tea fractions. 12-O-tetradecanoylphorbol-13-acetate-induced free radicals were inhibited by most tea fractions. These results provide strong evidence of both anti-mutagenic, anti-proliferative and anti-neoplastic activities for both black and green tea extracts. Such anticancer mechanisms may well be responsible for the cancer preventive efficacies seen in both experimental and human studies.     

Black tea polyphenols suppress cell proliferation and induce apoptosis during benzo(a)pyrene-induced lung carcinogenesis.

One of the most promising strategies for cancer prevention is chemoprevention by daily used food and beverages. Black tea, the most widely consumed beverage, is a source of compounds with antioxidative, antimicrobial, antimutagenic and anticarcinogenic properties. Lung cancer is the most common cause of cancer deaths in both men and women worldwide. Over one million people around the world are likely to be killed by lung cancer due to increased tobacco smoking and environmental pollutants, especially car exhausts. Therefore chemopreventive intervention using black tea and its active components may be a viable means to reduce lung cancer death. In the present investigation, we used benzo(a)pyrene (BP) to induce lung carcinogenesis in mice for the assessment of potential apoptosis-inducing and proliferation-suppressing effects of theaflavins and epigallocatechin gallate, active components of black tea. Hyperplasia, dysplasia and carcinoma in situ evident in the carcinogen control group on the 8th, 17th and 26th weeks respectively, were effectively reduced after treatment with theaflavins and epigallocatechin gallate. Significant reduction in number of proliferating cells and increased number of apoptotic cells was also found on the 8th, 17th and 26th week of treatment with theaflavins and epigallocatechin gallate in BP-exposed mice. Our observation suggests a promising role for black tea polyphenols in the prevention of lung cancer.     

Black tea protects immunocytes from tumor-induced apoptosis by changing Bcl-2/Bax ratio

It is known that cancer is associated with altered immune function. We demonstrated earlier that black tea inhibits tumor growth in a dose-dependent manner. Here, we report that apoptosis was the cause of immunocyte death in Ehrlich's ascites carcinoma (EAC)-bearing mice and anti-tumor dose of black tea restored EAC-induced immunosuppression by inhibiting apoptosis. A search for the molecular mechanism revealed that EAC burden increased the expression of the pro-apoptotic proteins p53 and Bax in splenic lymphocytes although did not change the level of pro-proliferative protein Bcl-2. Interestingly, anti-tumor dose of black tea down-regulated p53, decreased Bax while augmenting Bcl-2 in these cells. As a result, Bcl-2/Bax ratio was increased and the immunocytes were protected from tumor-induced apoptosis. Thus, unlike many other anti-cancer agents, black tea is not only devoid of immunosuppressive effect but also acts as immuno-restorer in tumor-bearing host. These results, thus, raise the possibility of inclusion of black tea in successful therapeutic regimen against cancer.