植物抗癌药紫杉醇的研究进展

癌症作为危害人类健康，导致人类死亡的主要疾病与病毒性疾病、老年性疾病并称为现代医学的三大挑战。抗癌药物的研发是当今的一个世界课题，特别是从天然产物中筛选抗癌新药，已成为抗癌药物研发的热点。自二十世纪50年代末期从长春花中发现抗癌活性成分长春碱以来，各国政府、药厂、科学家们运用各种方法从大量的植物中筛选抗癌活性成分，经抗肿瘤活性实验表明，这些活性成分都具有较强的抑制癌细胞增殖的效果。目前有些植物提取物已进入临床应用阶段，除了国内外研究和应用较多的农吉利、长春花、喜树、美登木、三尖杉、鸦胆子等抗癌植物以外，紫杉醇是过去数十年里发现的最好的天然抗癌药物之一，其独特的药理作用成为继阿霉素和顺铂后的热点抗癌新药。现就对紫杉醇的发现，作用机制，临床应用及不良反应等作一概述。     

天然产物抗癌研究进展

恶性肿瘤是现代社会威胁人类健康的重要杀手。合理有效的药物应用为恶性肿瘤治疗提供了有效手段,并有望成为未来解决肿瘤治疗难题的重要途径。近年来,随着肿瘤新理论的不断升级,以及肿瘤耐药等临床用药问题的不断涌现,创新的抗癌药物研发始终是肿瘤研究的热点和重点。其中,天然产物以其明确的抗癌有效性、候选资源的丰富性等优势,成为抗癌药物研发的重中之重。因此,在抗癌天然产物研究"热、多、杂"的背景下,条理化地归纳天然产物抗癌的进展,总结梳理其合理靶点及潜在机制,并在此基础上提示出未来进一步抗癌天然产物发展的新方向和新动态,是势在必行的。文章以肿瘤疾病进展的全链条为串联思路,以抗癌天然活性成分靶点的特征为切入点,着重从传统应用和创新应用两方面,对目前天然产物抗癌的研究进展进行总述。希望能够较为全面地揭示出天然产物抗癌的发展路径,并为抗癌药物的创新研发提供启示和思路。     

我国天然抗肿瘤药物的研究进展

恶性肿瘤是严重威胁人类健康的常见病和多发病,据世界卫生组织报告,全球50多亿人口中,每年新诊断的肿瘤患者约为900万人,因肿瘤而死亡者达700万人/a,占总病死率的近20%.药物治疗在恶性肿瘤的三大疗法中占有重要的地位, 发展速度最快.在合成的化学类抗癌药物中绝大多数都是以天然抗癌活性成分为先导化合物的,抗癌药物的开发,包括计算机模拟和仿生设计都是以天然抗癌活性成分为基础的.我国有丰富的药用植物资源, 自60年代以来我国的医药专家根据各民族运用天然抗癌药物的经验,从民族医药中研究和开发出了一批疗效确切、不良反应小的天然抗癌药物,为癌症的防治作出了应有的贡献.笔者以抗癌作用的机制为线索,对20世纪80年代以来我国研制的各类天然抗肿瘤药物作一扼要综述.……     

与微管作用的抗肿瘤天然产物的研究进展

自从紫杉醇广泛应用于临床治疗以来,与微管作用的抗肿瘤天然产物的发现、化学修饰和机制研究已经成为学术和临床研究的热点。介绍了与微管作用的抗肿瘤天然产物的研究情况,包括紫杉醇、埃博霉素、disco-dermolid、考布他汀、软海绵素、海兔毒素、那可丁等,简要探讨了目前存在的问题和未来的发展方向。     

天然药物化学史话:银杏内酯

天然药物不论过去还是现在都为人类的健康发展做出了重要贡献,近年来天然药物化学在新药研发中的作用又重新受到科学家的重视,天然产物的抗衰老研究也越来越受到关注。主要介绍天然来源的著名抗衰老药物银杏内酯的发现与研究历史,以纪念这一伟大发现以及为此研究做出贡献的科学家,同时期望为以后相关的研究以启示。     

紫杉醇的药理与临床研究进展

紫杉醇(Paclitaxel,商品名Taxol)是一种二萜类化合物,最早由Wani等[1]从短叶红豆杉(Taxus brevifo lia)的树皮中分离到并确定了其化学结构。自紫杉醇独特的抗癌机制揭示以来,紫杉醇的研究得到世界各国研究人员的重视,并相继证明其可以治疗卵巢癌、乳腺癌、子宫癌、肺癌、食管癌、前列腺癌以及直肠癌等十几种癌症。近年来,国内外的研究人员从不同角度对紫杉醇抗癌机制、临床应用等方面进行了研究,笔者现将这些方面的研究进展概述如下。1药理作用微管是真核细胞的一种组成成分,它是由2条类似的多氨基酸结合,促进微管蛋白聚合、微管装配,防止…     

抗癌植物药紫杉醇研究进展与动态

紫杉醇(paclitaxel,商品名Taxol)是一种在红豆杉科(Taxaceae L.)红豆杉属(Taxus L.)生长缓慢的长绿乔木中分离提取到的天然化合物.紫杉醇是目前全世界公认治疗肿瘤的有效药物,也是全球抗癌药物研究的热点.近年来,紫杉醇无论在药理活性、分离测定方法、提取纯化技术、化学结构修饰、类似物的化学结构及其生物活性和主要活性物质     

天然药物化学研究与新药开发

自从有人类历史以来,天然药物一直是人类防病治病的主要来源。天然产物是自然界的生物历经千百万年的进化过程通过自然选择保留下来的二次代谢产物,具有化学多样性、生物多样性和类药性。临床上应用的许多药物都直接或间接来源于天然产物,如天然产物可作为药物半合成的前体物、药物化学合成的模板以及为药物设计提供了新的思路。但是在20世纪80~90年代,由于受高通量筛选和组合化学的影响,天然药物的研究一度进入低谷。近10年来天然药物化学在新药研发中的作用又重新受到科学家的重视,天然产物已成为发现治疗重大疾病的药物或重要先导化合物的主要源泉之一。现就天然药物化学在新药开发中的作用进行了回顾与总结,并对其前景进行了展望。     

天然药物化学史话:天然产物研究与诺贝尔奖

天然产物化学仍是相当活跃的研究领域,天然产物化学研究者在诺贝尔化学奖获得者中始终占有相当比例。简要介绍在天然产物研究领域做出重要贡献而荣获诺贝尔奖的科学家,以介绍诺贝尔化学奖获得者为主,纪念他们的伟大功绩并借此激励有志于此领域科学研究的年轻工作者。     

天然药物化学史话:雷帕霉素

天然产物化学研究在药物研发中起着非常重要的作用。微生物是新药的主要来源之一,雷帕霉素就是一种从来自复活节岛土壤微生物中得到的化合物,它的发现引领了一系列免疫与抗癌药物的问世。科学家对雷帕霉素作用靶点的研究已取得了"诺贝尔奖级别"的成果。对雷帕霉素的研发历程进行回顾,期望能够为今后相关研究提供思路与启示。     

Nigerian antimalarial plants and their anticancer potential: A review

Cancer is a leading cause of death globally, while malaria is the leading cause of death from parasitic diseases in Nigeria. Historically, plant remedies have been used to manage both cancer and malaria. Interestingly, the possibility of treating cancer with antimalarial remedies has long been reported, even though the two diseases appear to have little in common. However, a body of research has indicated the potential anticancer activity of both synthetic and nature-derived antimalarials. In Nigeria, over 100 plants are used for the management of malaria, but little is known for their potential role in combatting cancer. Therefore, this review is to highlight the documented anticancer activities of plants used to treat malaria in Nigeria, with the goal of supporting anticancer drug discovery. Scientific databases were used to search for antimalarial plants using selected keywords. Of over 100 plants used to treat malaria in Nigeria, 56 have documented anticancer properties, containing alkaloids, flavonoids, tannins, terpenes, terpenoids, quinones, anthraquinones, saponins, steroids, sterols, organosulfur compounds and other polyphenols as the major bioactive components. The major mechanisms of anticancer activity include induction of apoptosis and autophagy, arrest of cell growth, generation of reactive oxygen species and inhibition of angiogenesis. However, mechanistic and clinical investigations of the anticancer properties of most of these plants are still lacking. Notwithstanding, the huge anticancer potential uncovered by the in vitro or in vivo studies and a few clinical studies, Nigerian antimalarial plants may provide a valuable resource, ready to be harnessed for anticancer drug development.     

中药逆转P-糖蛋白介导的肿瘤多药耐药的研究进展

多药耐（MDR）是导致癌症化疗失败的主要因素。肿瘤产生MDR的机制很多，其中最为常见也研究得较为深入的一种机制是一种ATP依赖跨膜转运蛋白P-糖蛋白（P—gp）在肿瘤细胞中的过度表达。由于相当一部分化疗药物属于P-gp的转运底物，过度表达的P-gp使细胞内药物浓度显著低于有效毒性浓度，从而产生耐药性。P-gp调节剂可通过抑制P—gp的转运功能或者抑制蛋白的表达修复肿瘤细胞对药物的敏感性。本文就近年来在部分中药及中药单体成分逆转肿瘤P-gp—MDR作用方面的研究做一些总结。     

Anticancer Properties of Solamargine: A Systematic Review

Cancers are usually treated by anticancer agents that are toxic for both normal and cancer cells, so these drugs have major side effects and they are not suitable and enough effective for cancer prevention. Solamargine, a steroidal alkaloid glycoside found in Solanum species such as Solanum nigrum, displayed several therapeutic activities. We aim to review the use of solamargine in experimental cancer studies. Articles published in biology journals between 1975 and 2017 were retrieved from PubMed, Scopus, and Web of Science using relevant keywords. The scientific papers mainly focusing on solamargine with therapeutic efficacies against cancers were identified and tabulated. In addition, the reliability of experimental findings was determined under “Risk of Bias” criteria. The author manually reviewed 33 articles; 27 articles were found concerning the anti‐cancer potential in cancer cells. Solamargine has been found to possess anticancer activities via its effect on a variety of biological pathways including cell survival pathways, tumor suppressor pathways, caspase activation pathway, mitochondrial pathways, death receptor pathways, protein kinase pathways, and signal pathways, which promote invasion/migration and multi drug resistance. Solamargine can be an anticancer agent candidate when complementary scientific evidences become available. Copyright © 2017 John Wiley & Sons, Ltd.     

Cinnamaldehydes in Cancer Chemotherapy

Cinnamaldehyde and cinnamaldehyde‐derived compounds are candidates for the development of anticancer drugs that have received extensive research attention. In this review, we summarize recent findings detailing the positive and negative aspects of cinnamaldehyde and its derivatives as potential anticancer drug candidates. Furthermore, we describe the in vivo pharmacokinetics and metabolism of cinnamaldehydes. The oxidative and antioxidative properties of cinnamaldehydes, which contribute to their potential in chemotherapy, have also been discussed. Moreover, the mechanism(s) by which cinnamaldehydes induce apoptosis in cancer cells have been explored. In addition, evidence of the regulatory effects of cinnamaldehydes on cancer cell invasion and metastasis has been described. Finally, the application of cinnamaldehydes in treating various types of cancer, including breast, prostate, and colon cancers, has been discussed in detail. The effects of cinnamaldehydes on leukemia, hepatocellular carcinoma, and oral cancer have been summarized briefly. Copyright © 2016 John Wiley & Sons, Ltd.     

Capsicum annuum L. and its bioactive constituents: A critical review of a traditional culinary spice in terms of its modern pharmacological potentials with toxicological issues

Capsicum annuum L., commonly known as chili pepper, is used as an important spice globally and as a crude drug in many traditional medicine systems. The fruits of C. annuum have been used as a tonic, antiseptic, and stimulating agent, to treat dyspepsia, appetites, and flatulence, and to improve digestion and circulation. The article aims to critically review the phytochemical and pharmacological properties of C. annuum and its major compounds. Capsaicin, dihydrocapsaicin, and some carotenoids are reported as the major active compounds with several pharmacological potentials especially as anticancer and cardioprotectant. The anticancer effect of capsaicinoids is mainly mediated through mechanisms involving the interaction of Ca²⁺-dependent activation of the MAPK pathway, suppression of NOX-dependent reactive oxygen species generation, and p53-mediated activation of mitochondrial apoptosis in cancer cells. Similarly, the cardioprotective effects of capsaicinoids are mediated through their interaction with cellular transient receptor potential vanilloid 1 channel, and restoration of calcitonin gene-related peptide via Ca²⁺-dependent release of neuropeptides and suppression of bradykinin. In conclusion, this comprehensive review presents detailed information about the traditional uses, phytochemistry, and pharmacology of major bioactive principles of C. annuum with special emphasis on anticancer, cardioprotective effects, and plausible toxic adversities along with food safety.     

Curcumin and tetrahydrocurcumin induce cell death in Ara‐C‐resistant acute myeloid leukemia

Most anticancer agents induce cancer cell death; however, multidrug‐resistant cancers often lead to treatment failure. The effective use of curcumin as an anticancer agent has been demonstrated in clinical trials. Tetrahydrocurcumin, a major curcumin metabolite, exhibits pharmacological activities similar to those of curcumin. Curcumin induces cell death mainly through the apoptosis pathway, and tetrahydrocurcumin induces cell death mainly via an autophagy pathway in HL60 cells. Here, we investigated whether curcumin and tetrahydrocurcumin can induce apoptosis‐ and autophagy‐mediated cell deaths in Ara‐C‐resistant cancer cells, respectively. The results demonstrated that curcumin and tetrahydrocurcumin induced cell death by apoptosis and autophagy, respectively, in Ara‐C‐resistant HL60 cells. Thus, curcumin and tetrahydrocurcumin have potential applications in the treatment of acute myeloid leukemia with Ara‐C resistance.     

An endophytic fungus from Nothapodytes foetida that produces camptothecin

A fungal endophytic isolate, camptothecin, has been isolated from the inner bark of the plant Nothapodytes foetidafrom the Western coast of India. The fungus, which belongs to the family Phycomycetes, produced the anticancer drug lead compound camptothecin (1) when grown in a synthetic liquid medium (Sabouraud broth) under shake flask and bench scale fermentation conditions. Compound 1 was identified by means of chromatographic and spectroscopic methods. It was also compared with an authentic example for its biological activity against a number of human cancer cell lines. Isolation of an organism producing 1 and its fermentation may, in the future, provide an easily accessible source for the production of this anticancer drug precursor molecule.     

Nanoformulations as a strategy to overcome the delivery limitations of cannabinoids

Medical cannabis has received significant interest in recent years due to its promising benefits in the management of pain, anxiety, depression and neurological and movement disorders. Specifically, the major phytocannabinoids derived from the cannabis plant such as (−) trans-Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been shown to be responsible for the pharmacological and therapeutic properties. Recently, these phytocannabinoids have also attracted special attention in cancer treatment due to their well-known palliative benefits in chemotherapy-induced nausea, vomiting, pain and loss of appetite along with their anticancer activities. Despite the enormous pharmacological benefits, the low aqueous solubility, high instability (susceptibility to extensive first pass metabolism) and poor systemic bioavailability restrict their utilization at clinical perspective. Therefore, drug delivery strategies based on nanotechnology are emerging to improve pharmacokinetic profile and bioavailability of cannabinoids as well as enhance their targeted delivery. Here, we critically review the nano-formulation systems engineered for overcoming the delivery limitations of native phytocannabinoids including polymeric and lipid-based nanoparticles (lipid nano capsules (LNCs), nanostructured lipid carriers (NLCs), nanoemulsions (NE) and self-emulsifying drug delivery systems (SEDDS)), ethosomes and cyclodextrins as well as their therapeutic applications.     

粉防己碱的抗肿瘤药理研究新进展

目的综述近年来粉防己碱抗肿瘤药理研究的最新进展，为其深入研究和开发提供参考。方法通过检索近年来的有关文献资料，进行整理和归纳。结果粉防己碱不仅能直接抑制多种肿瘤生长，并且具有放疗增敏、逆转耐药、减轻放化疗毒副反应的作用。其作用机制与诱导肿瘤细胞凋亡，下调MRP表达等有关。结论粉防己碱在抗肿瘤方面具有多种药理作用，具有广泛的开发前案。     

人参皂苷Rh2抗肝癌作用机制的研究进展

人参皂苷 Rh_2是一种含有达玛烷型骨架的四环三萜类皂苷单体,具有毒性低、相对分子质量小、脂溶性好、抗癌作用强等优势,是人参中主要的抗癌有效成分。近年来,有关人参皂苷 Rh_2的研究成果不断涌现,其对发病率和死亡率较高的多种癌症,均表现出明显的抗癌活性,其中人参皂苷 Rh_2抗肝癌的作用显著,因此关于抗肝癌作用机制的研究逐渐被人们重视。该文查阅中国知网,万方数据,维普数据,Pub Med等多个中英文数据库近20年来100余篇国内外相关文献资料,并对其中有关人参皂苷 Rh_2抗肝癌作用机制的内容进行详细的整理、归纳、分析和总结,发现虽然有关人参皂苷 Rh_2抗肝癌相关研究的报道不少,但是对于人参皂苷 Rh_2抗肝癌的作用机制没有进行系统的阐述,因此该文全面地探讨了人参皂苷 Rh_2抗肝癌的作用机制,明确了人参皂苷 Rh_2抗肝癌的作用机制可能与抑制肝癌细胞增殖、诱导肝癌细胞分化、促进肝癌细胞凋亡、抑制肝癌细胞侵袭与转移、降低肝癌细胞耐药性和提高机体免疫力等作用有关。首次对人参皂苷 Rh_2抗肝癌的作用机制进行较全面的整理,为科研人员开展有关人参皂苷 Rh_2抗肝癌的相关研究提供了参考和借鉴,为人参皂苷 Rh_2的进一步研究提供依据和思路,为肝癌的治疗提供新的研究方向,为肝癌患者带来了新希望。