anti-cancer activities

抗癌活性
  • 文章类型: Journal Article
    肝癌和乳腺癌被列为导致高癌症相关死亡率的最常见癌症。由于癌症是一种威胁生命的疾病,影响全球人口,需要开发新的疗法。在可用的治疗选择中包括放射治疗,化疗,手术,和免疫疗法。最先进的现代方法是使用植物衍生的抗癌药物,靶向癌细胞并抑制其增殖。植物衍生的化合物通常被认为比合成药物/传统疗法更安全,可以作为治疗肝癌和乳腺癌的潜在新靶点,彻底改变癌症治疗。生物碱和多酚已被证明通过分子方法充当抗癌剂。它们破坏各种细胞机制,抑制细胞周期蛋白和CDK的产生以阻止细胞周期,并通过上调p53,p21和p38的表达来激活DNA修复机制。在严重的情况下,当无法修复时,它们通过激活caspase-3、8和9并增加Bax/Bcl-2比率来诱导肝癌和乳腺癌细胞的凋亡。它们还使几种信号通路失活,如PI3K/AKT/mTOR,STAT3,NF-kB,嘘,MAPK/ERK,和Wnt/β-catenin途径,控制癌细胞的发展和转移。这篇综述的重点是对癌症中至关重要的特定蛋白质表达的调节,例如在HER2过表达的乳腺癌细胞中;生物碱和多酚已被报道降低HER2以及MMP表达。这项研究回顾了40多种具有针对肝癌和乳腺癌的特定分子靶标的植物性生物碱和多酚。其中,氧化苦参碱,Hirsutine,胡椒碱,Solamargine,和马钱子碱目前正在临床试验中,因为副作用较小,因此有资格作为有效的抗癌剂。由于对抗癌化合物的研究很多,人们迫切需要收集数据,以进入临床试验阶段4,并控制肝癌和乳腺癌的患病率。
    Liver and Breast cancer are ranked as the most prevailing cancers that cause high cancer-related mortality. As cancer is a life-threatening disease that affects the human population globally, there is a need to develop novel therapies. Among the available treatment options include radiotherapy, chemotherapy, surgery, and immunotherapy. The most superlative modern method is the use of plant-derived anticancer drugs that target the cancerous cells and inhibit their proliferation. Plant-derived compounds are generally considered safer than synthetic drugs/traditional therapies and could serve as potential novel targets to treat liver and breast cancer to revolutionize cancer treatment. Alkaloids and Polyphenols have been shown to act as anticancer agents through molecular approaches. They disrupt various cellular mechanisms, inhibit the production of cyclins and CDKs to arrest the cell cycle, and activate the DNA repairing mechanism by upregulating p53, p21, and p38 expression. In severe cases, when no repair is possible, they induce apoptosis in liver and breast cancer cells by activating caspase-3, 8, and 9 and increasing the Bax/Bcl-2 ratio. They also deactivate several signaling pathways, such as PI3K/AKT/mTOR, STAT3, NF-kB, Shh, MAPK/ERK, and Wnt/β-catenin pathways, to control cancer cell progression and metastasis. The highlights of this review are the regulation of specific protein expressions that are crucial in cancer, such as in HER2 over-expressing breast cancer cells; alkaloids and polyphenols have been reported to reduce HER2 as well as MMP expression. This study reviewed more than 40 of the plant-based alkaloids and polyphenols with specific molecular targets against liver and breast cancer. Among them, Oxymatrine, Hirsutine, Piperine, Solamargine, and Brucine are currently under clinical trials by qualifying as potent anticancer agents due to lesser side effects. As a lot of research is there on anticancer compounds, there is a desideratum to compile data to move towards clinical trials phase 4 and control the prevalence of liver and breast cancer.
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  • 文章类型: Journal Article
    从褐藻Stoechospermum边缘菌中分离出三种新的扇贝二萜(1-3)以及三种已知的化合物(4-6)。通过详细的NMR光谱和质谱分析确定这些化合物的结构。筛选了所有分离的化合物对一组四种人类癌细胞系的细胞毒性潜力,其中包括DU145(前列腺),B16F10(黑色素瘤),MDAMB-231(乳腺),和HeLa(宫颈)以及正常细胞系(HEK)。筛选结果表明,化合物1、4和5对B16F10[IC50,6.21±0.14,5.88±0.21,5.31±0.24μM]和MDAMB-231[9.25±0.61,4.59±0.14,4.19±0.13μM]细胞株均显示出显著的活性,分别。鉴于他们的重要活动,这些化合物1、4和5被进一步用于详细的荧光测定,划痕测定和流式细胞术分析,这表明它们在S期和G2/M期减少增殖并阻止细胞周期,通过凋亡诱导细胞死亡。总的来说,基于他们可观的成果,这些化合物可以作为抗癌候选药物开发的先导分子。
    Three new spatane diterpenoids (1-3) were isolated from the brown alga Stoechospermum marginatum together with three known compounds (4-6). The structures of these compounds were determined by the detailed NMR spectroscopic and Mass spectrometric analyses. All the isolated compounds were screened for their cytotoxic potentials against a panel of four human cancer cell lines, which include DU145 (Prostate), B16F10 (Melanoma), MDA MB-231 (Breast), and HeLa (Cervical) along with a normal cell line (HEK). The screening results indicated that compounds 1, 4 and 5 displayed significant activities against B16F10 [IC50, 6.21 ± 0.14, 5.88 ± 0.21, 5.31 ± 0.24 μM] and MDA MB-231 [9.25 ± 0.61, 4.59 ± 0.14, 4.19 ± 0.13 μM] cell lines, respectively. In view of their significant activity, these compounds 1, 4 and 5 were further taken up for detailed fluorescence assays, scratch assay and flow cytometry analysis, which revealed that they diminished proliferation and arrested cell cycle in the S phase and G2/M phase, which induced cell death by apoptosis. Overall, based on their considerable results, these compounds could serve as lead molecules in the development of anticancer drug candidates.
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  • 文章类型: Journal Article
    在弥漫性大B细胞淋巴瘤(DLBCL)患者中,原癌基因MYC经常失调,并在疾病进展中起关键作用。改善DLBCL患者的临床预后,制定针对MYC的战略至关重要。使用药用植物开发抗癌药物由于其不同的作用机制而引起了相当大的关注。在这项研究中,筛选了100种来自大韩民国的植物提取物,以寻找具有抗DLBCL作用的新型药物。其中,Ajaniapacifica(Nakai)K.Bremer和Humphries提取物(APKH)有效抑制DLBCL细胞的存活,同时对正常小鼠骨髓细胞毒性最小。APKH抑制抗凋亡BCL2家族成员的表达,导致促凋亡和抗凋亡BCL2成员之间的不平衡。这种破坏的线粒体膜电位,细胞色素c释放,和pro-caspase-3激活并最终导致DLBCL细胞死亡。重要的是,MYC表达被APKH显著下调,MYC在DLBCL细胞中的异位表达消除了APKH的促凋亡作用。这些结果证明APKH通过抑制MYC表达发挥抗DLBCL作用。此外,当与阿霉素联合使用时,CHOP方案的重要组成部分(环磷酰胺,阿霉素,长春新碱,和泼尼松),APKH协同增强阿霉素的治疗效果。这表明APKH可以克服耐药性,这在难治性/复发性DLBCL患者中很常见。为了鉴定APKH中具有抗DLBCL活性的化合物,使用UPLC-QTOF/MSe分析进行APKH的化学谱分析并评估其抗癌活性。基于UPLC-QTOF/MSe化学剖析,可以想象,APKH可能是靶向MYC并使耐药DLBCL细胞对CHOP化疗敏感的新型药物.有必要进一步研究阐明APKH中的化合物如何在DLBCL中发挥肿瘤抑制作用。
    The proto-oncogene MYC is frequently dysregulated in patients with diffuse large B-cell lymphoma (DLBCL) and plays a critical role in disease progression. To improve the clinical outcomes of patients with DLBCL, the development of strategies to target MYC is crucial. The use of medicinal plants for developing anticancer drugs has garnered considerable attention owing to their diverse mechanisms of action. In this study, 100 plant extracts of flora from the Republic of Korea were screened to search for novel agents with anti-DLBCL effects. Among them, Ajania pacifica (Nakai) K. Bremer and Humphries extract (APKH) efficiently suppressed the survival of DLBCL cells, while showing minimal toxicity toward normal murine bone marrow cells. APKH suppressed the expression of anti-apoptotic BCL2 family members, causing an imbalance between the pro-apoptotic and anti-apoptotic BCL2 members. This disrupted mitochondrial membrane potential, cytochrome c release, and pro-caspase-3 activation and eventually led to DLBCL cell death. Importantly, MYC expression was markedly downregulated by APKH and ectopic expression of MYC in DLBCL cells abolished the pro-apoptotic effects of APKH. These results demonstrate that APKH exerts anti-DLBCL effects by inhibiting MYC expression. Moreover, when combined with doxorubicin, an essential component of the CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), APKH synergistically enhanced the therapeutic effect of doxorubicin. This indicates that APKH may overcome drug resistance, which is common in patients with refractory/relapsed DLBCL. To identify compounds with anti-DLBCL activities in APKH, the chemical profile analysis of APKH was performed using UPLC-QTOF/MSe analysis and assessed for its anticancer activity. Based on the UPLC-QTOF/MSe chemical profiling, it is conceivable that APKH may serve as a novel agent targeting MYC and sensitizing drug-resistant DLBCL cells to CHOP chemotherapy. Further studies to elucidate how the compounds in APKH exert tumor-suppressive role in DLBCL are warranted.
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  • 文章类型: Journal Article
    一品红是一品红科的一个大属。在化学和药理学上研究了大约250种大品藻属;从这些物种中分离出不同的化合物,尤其是二萜和三萜.一些报告显示,几种物种具有抗炎活性,这可以归因于二萜的存在,例如abietanes,ingenanes,和lathyranes。此外,发现从不同一品红种分离的一些二萜具有抗癌活性。在这次审查中,我们纳入了从2018年至2023年9月发表的具有抗炎或细胞毒性作用的一品红属物种中分离出的化合物.这篇综述使用的数据库是科学直接,Scopus,PubMed,Springer,和谷歌学者,使用具有抗炎或细胞毒性活性的关键字Euphorbia。在这次审查中,收集并分析了68项研究,这些研究涉及从36种大猩猩属物种获得的264种化合物的抗炎和抗癌活性。本综述中包括的化合物是萜烯(95%),其中68%是二萜,尤其是ingenanes的类型,abietanes,和三萜(约15%)。
    Euphorbia is a large genus of the Euphorbiaceae family. Around 250 species of the Euphorbia genus have been studied chemically and pharmacologically; different compounds have been isolated from these species, especially diterpenes and triterpenes. Several reports show that several species have anti-inflammatory activity, which can be attributed to the presence of diterpenes, such as abietanes, ingenanes, and lathyranes. In addition, it was found that some diterpenes isolated from different Euphorbia species have anti-cancer activity. In this review, we included compounds isolated from species of the Euphorbia genus with anti-inflammatory or cytotoxic effects published from 2018 to September 2023. The databases used for this review were Science Direct, Scopus, PubMed, Springer, and Google Scholar, using the keywords Euphorbia with anti-inflammatory or cytotoxic activity. In this review, 68 studies were collected and analyzed regarding the anti-inflammatory and anti-cancer activities of 264 compounds obtained from 36 species of the Euphorbia genus. The compounds included in this review are terpenes (95%), of which 68% are diterpenes, especially of the types ingenanes, abietanes, and triterpenes (approximately 15%).
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  • 文章类型: Journal Article
    最近,硒纳米颗粒已经引起了全世界的关注,提高纳米硒的稳定性至关重要。巴林达多糖(MOP)是巴林达的主要活性成分。然而,它们的低活性限制了它们的应用。为了解决这些问题,使用MOP作为分散剂制备了一种新型的硒纳米颗粒(Se-MOP)。测量ζ电位以评估稳定性,采用UV和ATR-FTIR研究了硒与MOP的结合类型。通过TEM方法观察形态。此外,对五种选定的癌细胞(HepG2,MCF-7,AGS,PC9和HCT8)进行了评估,对所有五种癌细胞都有显著的抑制作用。还通过细胞周期测定研究了抑制的机制,发现Se-MOP可以诱导细胞周期G0/G1期阻滞。通过体外测定小鼠脾淋巴细胞的增殖和细胞因子并进行定量RT-PCR来评估免疫增强活性。结果表明,Se-MOP的单次刺激和PHA或LPS的协同刺激可通过增加细胞因子的表达来增加免疫能力并改善免疫力。
    Recently, selenium nanoparticles have been drawing attention worldwide, and it is crucial to increase the stability of nano-Se. Morinda officinalis polysaccharides (MOP) are the main active component in Morinda officinalis radix. However, their low activity has limited their application. A novel selenium nanoparticle (Se-MOP) was prepared to solve these problems using MOP as a dispersant. The zeta potential was measured to evaluate the stability, and UV and ATR-FTIR were used to investigate the binding type of selenium and MOP. The morphology was observed by the TEM method. Furthermore, the inhibitory effect on five selected cancer cells (HepG2, MCF-7, AGS, PC9, and HCT8) was evaluated, showing remarkable inhibition of all five cancer cells. The mechanism of inhibition was also investigated by cell circle assay, and it was found that Se-MOP could induce cell circle G0/G1 phase arrest. Immune-enhancing activities were evaluated by measuring the proliferation and cytokines of mouse spleen lymphocytes in vitro and quantitative RT-PCR. The results indicated that single stimulation of Se-MOP and synergistic stimulation with PHA or LPS increased immune capacity and improved immune by increasing the expression of cytokines.
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  • 文章类型: Journal Article
    中华鬼兰(Royle)T.S.Ying,鬼臼毒素(PTOX)的重要来源,由于过度收获,已经成为一种珍稀濒危植物。体细胞胚发生(SE)是幼苗快速繁殖和种质改良的主要途径,但是Hexandrum的再生还没有得到很好的证实,不同SE阶段的PTOX生物合成能力尚不清楚。因此,阐明六甘草的SE机制和阐明PTOX的生物合成变异极为重要。在这项研究中,对不同SE阶段的六角形链球菌转录组进行测序,测定了PTOX和4'-去甲基吡虫啉的含量,并通过qRT-PCR验证转录本的表达模式。结果表明,植物激素(如生长素、脱落酸,zeatin,赤霉素)相关通路在不同SE阶段显著富集,表明这些植物激素在六雄酵母SE中起着重要作用;胚性愈伤组织中一系列与PTOX生物合成相关的基因的表达水平以及PTOX和4'-去甲基吡虫啉毒素含量远高于其他阶段,表明胚性愈伤组织阶段在不同SE阶段中具有最佳的PTOX生物合成能力。本研究将有助于六角形的种质资源保存和快速繁殖。促进PTOX的生产。
    Sinopodophyllum hexandrum (Royle) T. S. Ying, an important source of podophyllotoxin (PTOX), has become a rare and endangered plant because of over-harvesting. Somatic embryogenesis (SE) is the main way of seedling rapid propagation and germplasm enhancement, but the regeneration of S. hexandrum has not been well established, and the PTOX biosynthesis abilities at different SE stages remain unclear. Therefore, it is extremely important to elucidate the SE mechanism of S. hexandrum and clarify the biosynthesis variation of PTOX. In this study, the transcriptomes of S. hexandrum at different SE stages were sequenced, the contents of PTOX and 4\'-demethylepipodophyllotoxin were assayed, and the transcript expression patterns were validated by qRT-PCR. The results revealed that plant hormone (such as auxins, abscisic acid, zeatin, and gibberellins) related pathways were significantly enriched among different SE stages, indicating these plant hormones play important roles in SE of S. hexandrum; the expression levels of a series of PTOX biosynthesis related genes as well as PTOX and 4\'-demethylepipodophyllotoxin contents were much higher in embryogenic callus stage than in the other stages, suggesting embryogenic callus stage has the best PTOX biosynthesis ability among different SE stages. This study will contribute to germplasm conservation and fast propagation of S. hexandrum, and facilitate the production of PTOX.
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  • 文章类型: Journal Article
    有忧郁症(W.somnifera)是一种具有显着的药理特性的植物。该植物在几种文明的民间医学系统中具有令人印象深刻的药用特征。
    这项全面的研究旨在表征W.somnifera果实中的植物化学物质,并测试抗癌潜力,以找出疾病预防和治疗中的活性候选物。
    用极性和非极性溶剂提取W.somn-ifera果实中的生物活性成分。通过MTT测定和Incucytes成像分析,针对不同的癌细胞系评估了分离的生物活性物质的抗癌潜力。使用GC-MS(气相色谱-质谱仪)表征提取物的次级代谢产物,LCMS(液相色谱-质谱)-ESI(电喷雾电离)和1H-NMR(电喷雾电离)技术。
    冷冻干燥和旋转蒸发仪浓缩的提取物均显示出对MDA-MB-231,MCF7-SKOV3和SKBR3细胞系的抗癌潜力。测试的提取物对哺乳动物癌细胞系具有细胞生长抑制潜力。通过使用Incucytes成像分析,研究了通过HPLC从-己烷提取物中纯化的六烷二酸对乳腺癌细胞系SKBR3的细胞毒性。
    我们发现该植物中存在多种生物活性化合物。纯化了一种在先前研究中未研究细胞毒性的鉴定化合物,其应用显示了对乳腺癌细胞系的细胞毒性。从水果中鉴定出的许多生物活性物质可能具有开发成化疗药物的有效潜力。
    Withania somnifera (W. somnifera) is a plant with remarkable pharmacological properties. The plant has an impressive profile of medicinal uses in the folk medicine system of several civilizations.
    This comprehensive study is aimed to characterize phytochemicals in fruit of W. somnifera and tested for anticancer potential to find out active candidate in disease prevention and treatment.
    The bioactive components from W. somn-ifera fruit were extracted with polar and non-polar solvents. Anticancer potential of the isolated bioactive was assessed against different cancer cell lines through MTT assay and Incucytes imaging analysis. The extracts were characterized for secondary metabolites using GC-MS (gas chromatography-mass spectrometer), LCMS (liquid chromatography-mass spectrometry)-ESI (electrospray Ionization) and 1H-NMR (electrospray Ionization) techniques.
    Both freeze-dried and rotary evaporator con-densed extracts exhibited anticancer potential against MDA-MB-231, MCF7- SKOV3 and SKBR3 cell lines. The tested extracts have cell growth inhibition potential ag-ainst mammalian cancer cell line. Hexacosanedioic acid purified from -hexane extract through HPLC was inves-tigated for its cytotoxicity against breast cancer cell line SKBR3 by using Incucytes imaging analysis.
    We found that a variety of bioactive compounds existed in this plant. One identified compound that was not investigated for cytotoxicity in previous studies was purified and its application showed cytotoxicity on breast cancer cell lines. A number of bioactive identified from fruit may have an effective potential for development into chemotherapy drugs.
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  • 文章类型: Journal Article
    Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant\'s diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.
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  • 文章类型: Journal Article
    藤黄酸(GA),藤黄树分泌的一种干树脂,是一种具有多种生物活性的天然活性成分,比如抗癌,抗炎,抗氧化剂,抗菌作用,等。越来越多的证据表明,GA通过各种分子机制具有明显的抗癌作用,包括细胞凋亡的诱导,自噬,细胞周期停滞和入侵的抑制,转移,血管生成。为了提高癌症治疗的疗效,纳米药物递送系统已被用于负载GA并形成胶束,纳米粒子,纳米纤维,等等。在这次审查中,我们的目标是提供化学结构和性质的总结,抗癌活动,药物递送系统和GA的联合治疗,为促进GA的发展和临床应用提供参考。
    Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers, and so on. In this review, we aim to offer a summary of chemical structure and properties, anti-cancer activities, drug delivery systems and combination therapy of GA, which might provide a reference to promote the development and clinical application of GA.
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  • 文章类型: Journal Article
    Hairy root induction in Plantago lanceolata was optimized to take advantage of transformed root cultures. The highest frequency of transformation was achieved using leaf explant, A4 strain, pre-cultivation of explant, 150 µM Acetosyringone, 5 min inoculation, half-strength Murashige and Skoog basal medium as co-cultivation, and half-strength Gamborg\'s basal medium as a selective medium with 3% sucrose. Among the studied compound encompassing gallic acid, catalpol and apigenin, only the production of gallic acid in hairy roots was affected by 20 mg L-1 AgNO3 and 100 mg L-1 chitosan at 24 hr which yielded 7.63, 4.76-fold increase in its content, respectively. The methanolic extracts of hairy roots elicited by 20 mg L-1 AgNO3 exhibited anti-bacterial activity (MIC and MBC = 25 mg mL-1) against Klebsiella pneumoniae, Proteus vulgaris and Salmonella typhi and anti-bacterial potential of non-elicited hairy roots of P. lanceolata (MIC = 25 mg mL-1 and MBC = 35 mg mL-1) were more active against Klebsiella pneumoniae and P. vulgaris than other bacteria. The methanolic extracts of the P. lanceolata hairy roots demonstrated significant cytotoxic activity on colorectal carcinoma cell line (SW-480) with IC50 = 250.65 ± 6.8 µg mL-1 in comparison to human embryonic kidney (HEK-293) with IC50 = 5263.65 ± 4.6 µg mL-1. Plantago lanceolata hairy roots showed important biological activity explaining its role in traditional medicine.
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