Potential target and mechanism exploration from α-mangostin against triple-negative breast cancer: An in silico study.

IF 1.4 Q3 Pharmacology, Toxicology and Pharmaceutics
Rafly Mochamad Rivaldo, Paulus Chandra
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引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) is one of the most common types of serious breast cancer. Due to the absence of therapeutic hormone receptors, TNBC treatment generally involves chemotherapy which results in various side effects and resistance development. Herbal compounds, including α-mangostin, have shown potential anticancer effects against TNBC. However, rigorous screening is needed to uncover its mechanisms and characteristics. The aim of this study was to understand the molecular mechanism of α-mangostin against TNBC and its possible limitations. The study design used is an in si lico study. The study involved database mining and compound characteristic analysis. Network pharmacology and molecular docking were also done to explore potential target and molecular mechanisms against TNBC. There was no statistical analysis conducted as this study relies on predefined algorithms and simulation models. Instead, a parameter threshold was used for each analysis to ensure its reliability. Prediction of Activity Spectra for Substances prediction and Gene Ontology-Kyoto Encyclopedia of Genes and Genomes enrichment predicted potential anticancer effects of α-mangostin through the regulation of enzyme activity and apoptotic pathway. Compound property predictions showed α-mangostin to have promising drug-likeness with sufficient bioavailability and low biodegradability. However, α-mangostin still has some potential limitations in water solubility and toxicity risks. Through network pharmacology, 75 potential target proteins of α-mangostin in TNBC cases were found. The top three most significant of which (AKT1, CTNNB1, and HSPAA91) were proven to bind with α-mangostin through molecular docking. Study results suggested α-mangostin to have a promising anticancer and chemopreventive activity with great drug-likeness and pharmacokinetic properties. It was revealed that α-mangostin can bind to key components in TNBC-related pathways, including AKT1, CTNNB1, and HSP90AA1 proteins. However, further experimental studies may be needed to verify its effectiveness as well as possible solubility and toxicity limitations.

α-曼戈斯汀抗三阴性乳腺癌的潜在靶点和机制探索:硅学研究
三阴性乳腺癌(TNBC)是最常见的严重乳腺癌类型之一。由于缺乏治疗性激素受体,TNBC 的治疗通常涉及化疗,而化疗会导致各种副作用和耐药性的产生。包括α-曼戈斯汀在内的草药化合物已显示出对TNBC的潜在抗癌作用。然而,要揭示其机制和特性,还需要进行严格的筛选。本研究旨在了解α-曼戈斯汀对TNBC的分子机制及其可能的局限性。本研究采用的研究设计是一项室内研究。研究涉及数据库挖掘和化合物特征分析。还进行了网络药理学和分子对接,以探索抗 TNBC 的潜在靶点和分子机制。由于该研究依赖于预定义的算法和模拟模型,因此没有进行统计分析。相反,每次分析都使用了一个参数阈值,以确保其可靠性。物质活性谱预测和基因本体-京都基因和基因组百科全书富集预测了α-曼戈斯汀通过调控酶活性和细胞凋亡途径的潜在抗癌作用。化合物性质预测显示,α-曼戈斯汀具有良好的药物相似性、足够的生物利用度和较低的生物降解性。然而,α-曼戈斯汀在水溶性和毒性风险方面仍有一些潜在的局限性。通过网络药理学研究,发现了α-曼戈斯汀在TNBC病例中的75个潜在靶蛋白。通过分子对接,证明了其中最重要的前三个蛋白(AKT1、CTNNB1和HSPAA91)与α-曼戈斯汀结合。研究结果表明,α-曼戈斯汀具有良好的抗癌和化学预防活性,并具有很好的药物亲和性和药代动力学特性。研究发现,α-曼戈斯汀能与AKT1、CTNNB1和HSP90AA1蛋白等TNBC相关通路中的关键成分结合。不过,可能还需要进一步的实验研究来验证其有效性以及可能存在的溶解性和毒性限制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.00
自引率
7.10%
发文量
44
审稿时长
20 weeks
期刊介绍: Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is an Official Publication of Society of Pharmaceutical Education & Research™. It is an international journal published Quarterly. Journal of Advanced Pharmaceutical Technology & Research (JAPTR) is available in online and print version. It is a peer reviewed journal aiming to communicate high quality original research work, reviews, short communications, case report, Ethics Forum, Education Forum and Letter to editor that contribute significantly to further the scientific knowledge related to the field of Pharmacy i.e. Pharmaceutics, Pharmacology, Pharmacognosy, Pharmaceutical Chemistry. Articles with timely interest and newer research concepts will be given more preference.
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