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非洲中部、东部和西部药用植物在癌症治疗中的潜力:聚焦耐药细胞和分子靶点

Potential of Central, Eastern and Western Africa Medicinal Plants for Cancer Therapy: Spotlight on Resistant Cells and Molecular Targets.

作者信息

Mbaveng Armelle T, Kuete Victor, Efferth Thomas

机构信息

Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of MainzMainz, Germany.

Department of Biochemistry, Faculty of Science, University of DschangDschang, Cameroon.

出版信息

Front Pharmacol. 2017 Jun 2;8:343. doi: 10.3389/fphar.2017.00343. eCollection 2017.

Abstract

Cancer remains a major health hurdle worldwide and has moved from the third leading cause of death in the year 1990 to second place after cardiovascular disease since 2013. Chemotherapy is one of the most widely used treatment modes; however, its efficiency is limited due to the resistance of cancer cells to cytotoxic agents. The present overview deals with the potential of the flora of Central, Eastern and Western African (CEWA) regions as resource for anticancer drug discovery. It also reviews the molecular targets of phytochemicals of these plants such as ABC transporters, namely P-glycoprotein (P-gp), multi drug-resistance-related proteins (MRPs), breast cancer resistance protein (BCRP, ABCG2) as well as the epidermal growth factor receptor (EGFR/ErbB-1/HER1), human tumor suppressor protein p53, caspases, mitochondria, angiogenesis, and components of MAP kinase signaling pathways. Plants with the ability to preferentially kills resistant cancer cells were also reported. Data compiled in the present document were retrieved from scientific websites such as PubMed, Scopus, Sciencedirect, Web-of-Science, and Scholar Google. In summary, plant extracts from CEWA and isolated compounds thereof exert cytotoxic effects by several modes of action including caspases activation, alteration of mitochondrial membrane potential (MMP), induction of reactive oxygen species (ROS) in cancer cells and inhibition of angiogenesis. Ten strongest cytotoxic plants from CEWA recorded following screening assays are: Kosterm, var. lelyi (C. D. Adams) A. Rich., Hua (Fabaceae), Beauv. var. koenigii Durand et Schinz, (Pobég. ex Pellegr.) Merr. ex E.M.A., L.f., (Hiern) Harms., Pax., Engl. and (Dunal) A. Rich. Prominent antiproliferative compounds include: isoquinoline alkaloid isotetrandrine (), two benzophenones: guttiferone E () and isoxanthochymol (), the isoflavonoid 6α-hydroxyphaseollidin (), the naphthyl butenone guieranone A (), two naphthoquinones: 2-acetylfuro-1,4-naphthoquinone () and plumbagin () and xanthone V (). However, only few research activities in the African continent focus on cytotoxic drug discovery from botanicals. The present review is expected to stimulate further scientific efforts to better valorize the African flora.

摘要

癌症仍然是全球主要的健康障碍,已从1990年的第三大死因升至2013年以来仅次于心血管疾病的第二位。化疗是最广泛使用的治疗方式之一;然而,由于癌细胞对细胞毒性药物的耐药性,其疗效有限。本综述探讨了中非、东非和西非(CEWA)地区植物群作为抗癌药物发现资源的潜力。它还回顾了这些植物的植物化学物质的分子靶点,如ABC转运蛋白,即P-糖蛋白(P-gp)、多药耐药相关蛋白(MRPs)、乳腺癌耐药蛋白(BCRP,ABCG2)以及表皮生长因子受体(EGFR/ErbB-1/HER1)、人类肿瘤抑制蛋白p53、半胱天冬酶、线粒体、血管生成和丝裂原活化蛋白激酶信号通路的组成部分。还报道了具有优先杀死耐药癌细胞能力的植物。本文件汇编的数据来自科学网站,如PubMed、Scopus、Sciencedirect、Web-of-Science和谷歌学术。总之,CEWA地区的植物提取物及其分离的化合物通过多种作用方式发挥细胞毒性作用,包括半胱天冬酶激活、线粒体膜电位(MMP)改变、癌细胞中活性氧(ROS)的诱导和血管生成的抑制。经筛选试验后记录的CEWA地区最强的十种细胞毒性植物为:Kosterm, var. lelyi (C. D. Adams) A. Rich., Hua (豆科), Beauv. var. koenigii Durand et Schinz, (Pobég. ex Pellegr.) Merr. ex E.M.A., L.f., (Hiern) Harms., Pax., Engl. 和 (Dunal) A. Rich. 突出的抗增殖化合物包括:异喹啉生物碱异粉防己碱()、两种二苯甲酮:藤黄双黄酮E()和异氧杂环春黄醇()、异黄酮6α-羟基菜豆素()、萘基丁烯酮桂兰酮A()、两种萘醌:2-乙酰基呋喃-1,4-萘醌()和白花丹素()以及呫吨酮V()。然而,非洲大陆只有少数研究活动专注于从植物中发现细胞毒性药物。本综述有望激发进一步的科学努力,以更好地利用非洲植物群。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6445/5454075/45e885fc5509/fphar-08-00343-g0001.jpg

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