{"title":"网络药理学、分子对接和分子动力学模拟揭示了Nauclea Latifolia治疗乳腺癌的分子靶点和潜在机制","authors":"Cromwel Tepap Zemnou","doi":"10.1002/cbdv.202402423","DOIUrl":null,"url":null,"abstract":"<p><p>Breast cancer (BRCA) incidence is increasing, posing a significant public health challenge and necessitating effective treatment solutions. Nauclea latifolia (N. latifolia) has shown anticancer activity against multidrug-resistant BRCA cells, though its mechanism of action remains unclear. We used online databases Swiss target prediction and GeneCards to identify therapeutic targets for BRCA and active compounds in N. latifolia. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Molecular docking, gene expression and survival analyses of core targets were conducted using Autodock 4.0 and GEPIA2 database. We identified 141 intersecting targets for BRCA and N. latifolia compounds, with key targets including ALB, AKT1, ESR1, STAT3, EGFR, SRC, PTGS2, GSK3B, MMP9, and PPAR1. These targets are involved in cell proliferation and death through pathways such as the PI3K-Akt signaling system, metabolic pathways, cancer pathways, and proteoglycans in cancer. Gene expression and survival analysis indicated these targets as potential markers for BRCA treatment prognosis. This study provides insights into the mechanism of action of N. latifolia against BRCA cells and give a basis to clinicians for future drug development.</p>","PeriodicalId":9878,"journal":{"name":"Chemistry & Biodiversity","volume":" ","pages":"e202402423"},"PeriodicalIF":2.3000,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Revealed the Molecular Targets and Potential Mechanism of Nauclea Latifolia in the Treatment of Breast Cancer.\",\"authors\":\"Cromwel Tepap Zemnou\",\"doi\":\"10.1002/cbdv.202402423\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Breast cancer (BRCA) incidence is increasing, posing a significant public health challenge and necessitating effective treatment solutions. Nauclea latifolia (N. latifolia) has shown anticancer activity against multidrug-resistant BRCA cells, though its mechanism of action remains unclear. We used online databases Swiss target prediction and GeneCards to identify therapeutic targets for BRCA and active compounds in N. latifolia. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Molecular docking, gene expression and survival analyses of core targets were conducted using Autodock 4.0 and GEPIA2 database. We identified 141 intersecting targets for BRCA and N. latifolia compounds, with key targets including ALB, AKT1, ESR1, STAT3, EGFR, SRC, PTGS2, GSK3B, MMP9, and PPAR1. These targets are involved in cell proliferation and death through pathways such as the PI3K-Akt signaling system, metabolic pathways, cancer pathways, and proteoglycans in cancer. Gene expression and survival analysis indicated these targets as potential markers for BRCA treatment prognosis. This study provides insights into the mechanism of action of N. latifolia against BRCA cells and give a basis to clinicians for future drug development.</p>\",\"PeriodicalId\":9878,\"journal\":{\"name\":\"Chemistry & Biodiversity\",\"volume\":\" \",\"pages\":\"e202402423\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-11-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemistry & Biodiversity\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1002/cbdv.202402423\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemistry & Biodiversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1002/cbdv.202402423","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
乳腺癌(BRCA)发病率不断上升,对公共卫生构成了重大挑战,需要有效的治疗方案。花叶女贞(Nauclea latifolia)对耐多药的 BRCA 细胞具有抗癌活性,但其作用机制仍不清楚。我们利用在线数据库瑞士靶点预测和基因卡片来确定 BRCA 的治疗靶点和 N. latifolia 的活性化合物。利用 STRING 数据库和 Cytoscape 构建了蛋白质-蛋白质相互作用(PPI)网络。利用 DAVID 数据库进行了基因本体(GO)和京都基因组百科全书(KEGG)通路富集分析。使用 Autodock 4.0 和 GEPIA2 数据库对核心靶点进行了分子对接、基因表达和存活分析。我们确定了 BRCA 和 N. latifolia 复合物的 141 个交叉靶点,主要靶点包括 ALB、AKT1、ESR1、STAT3、表皮生长因子受体、SRC、PTGS2、GSK3B、MMP9 和 PPAR1。这些靶点通过 PI3K-Akt 信号系统、代谢途径、癌症途径和癌症中的蛋白聚糖等途径参与细胞增殖和死亡。基因表达和生存分析表明,这些靶点是 BRCA 治疗预后的潜在标志物。这项研究深入揭示了 N. latifolia 对 BRCA 细胞的作用机制,为临床医生未来的药物开发提供了依据。
Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Revealed the Molecular Targets and Potential Mechanism of Nauclea Latifolia in the Treatment of Breast Cancer.
Breast cancer (BRCA) incidence is increasing, posing a significant public health challenge and necessitating effective treatment solutions. Nauclea latifolia (N. latifolia) has shown anticancer activity against multidrug-resistant BRCA cells, though its mechanism of action remains unclear. We used online databases Swiss target prediction and GeneCards to identify therapeutic targets for BRCA and active compounds in N. latifolia. Protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Molecular docking, gene expression and survival analyses of core targets were conducted using Autodock 4.0 and GEPIA2 database. We identified 141 intersecting targets for BRCA and N. latifolia compounds, with key targets including ALB, AKT1, ESR1, STAT3, EGFR, SRC, PTGS2, GSK3B, MMP9, and PPAR1. These targets are involved in cell proliferation and death through pathways such as the PI3K-Akt signaling system, metabolic pathways, cancer pathways, and proteoglycans in cancer. Gene expression and survival analysis indicated these targets as potential markers for BRCA treatment prognosis. This study provides insights into the mechanism of action of N. latifolia against BRCA cells and give a basis to clinicians for future drug development.
期刊介绍:
Chemistry & Biodiversity serves as a high-quality publishing forum covering a wide range of biorelevant topics for a truly international audience. This journal publishes both field-specific and interdisciplinary contributions on all aspects of biologically relevant chemistry research in the form of full-length original papers, short communications, invited reviews, and commentaries. It covers all research fields straddling the border between the chemical and biological sciences, with the ultimate goal of broadening our understanding of how nature works at a molecular level.
Since 2017, Chemistry & Biodiversity is published in an online-only format.