Chrysin: A Potential Antiandrogen Ligand to Mutated Androgen Receptors in Prostate Cancer.

Ahtziri Socorro Carranza-Aranda, Anne Santerre, Aldo Segura-Cabrera, Albertina Cárdenas-Vargas, Moisés Martínez-Velázquez, Rodolfo Hernández-Gutiérrez, Sara Elisa Herrera-Rodríguez
{"title":"Chrysin: A Potential Antiandrogen Ligand to Mutated Androgen Receptors in Prostate Cancer.","authors":"Ahtziri Socorro Carranza-Aranda, Anne Santerre, Aldo Segura-Cabrera, Albertina Cárdenas-Vargas, Moisés Martínez-Velázquez, Rodolfo Hernández-Gutiérrez, Sara Elisa Herrera-Rodríguez","doi":"10.2174/0118761429350210250102131611","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Androgen receptor mutations, particularly T877A and W741L, promote prostate cancer (PCa). The main therapies against PCa use androgen receptor (AR) antagonists, including Bicalutamide; but these drugs lose their effectiveness over time. Chrysin is a flavonoid with several biological activities, including antitumoral properties; however, its potential as an antiandrogen must be explored.</p><p><strong>Objective: </strong>The present study aimed to characterize and compare the molecular interactions of chrysin with wild-type and mutated ARs and their cytotoxic effect in an in vitro model of PCa.</p><p><strong>Methods: </strong>The affinities and molecular interactions of Bicalutamide and chrysin for the wild-type and mutated forms of AR were assessed by molecular docking. The MTT assay was used to evaluate the cytotoxic effect of these ligands on the DU-145 (T877A) and PC3 (W741L) PCa cell lines and on non-tumoral RWPE-1 cells.</p><p><strong>Results: </strong>The molecular dockings predicted a higher affinity of chrysin for the mutated AR than the wild-type AR (WT-AR); meanwhile, Bicalutamide presented a higher affinity for WT-AR. The amino acid residues involved in molecular interactions within the binding site of these receptors changed according to the ligands and AR variants, affecting their affinity scores and biological effects (agonist/antagonists). Chrysin exerted a specific cytotoxic effect against the PCa tumoral cells but none against the non-tumoral cells. In contrast, Bicalutamide showed potent cytotoxicity against all cell lines.</p><p><strong>Conclusion: </strong>This study evidences the potential antiandrogen effect of chrysin on mutated AR and specific cytotoxicity against PCa cells, suggesting that this flavonoid could be considered for PCa therapy.</p>","PeriodicalId":93964,"journal":{"name":"Current molecular pharmacology","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular pharmacology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118761429350210250102131611","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Androgen receptor mutations, particularly T877A and W741L, promote prostate cancer (PCa). The main therapies against PCa use androgen receptor (AR) antagonists, including Bicalutamide; but these drugs lose their effectiveness over time. Chrysin is a flavonoid with several biological activities, including antitumoral properties; however, its potential as an antiandrogen must be explored.

Objective: The present study aimed to characterize and compare the molecular interactions of chrysin with wild-type and mutated ARs and their cytotoxic effect in an in vitro model of PCa.

Methods: The affinities and molecular interactions of Bicalutamide and chrysin for the wild-type and mutated forms of AR were assessed by molecular docking. The MTT assay was used to evaluate the cytotoxic effect of these ligands on the DU-145 (T877A) and PC3 (W741L) PCa cell lines and on non-tumoral RWPE-1 cells.

Results: The molecular dockings predicted a higher affinity of chrysin for the mutated AR than the wild-type AR (WT-AR); meanwhile, Bicalutamide presented a higher affinity for WT-AR. The amino acid residues involved in molecular interactions within the binding site of these receptors changed according to the ligands and AR variants, affecting their affinity scores and biological effects (agonist/antagonists). Chrysin exerted a specific cytotoxic effect against the PCa tumoral cells but none against the non-tumoral cells. In contrast, Bicalutamide showed potent cytotoxicity against all cell lines.

Conclusion: This study evidences the potential antiandrogen effect of chrysin on mutated AR and specific cytotoxicity against PCa cells, suggesting that this flavonoid could be considered for PCa therapy.

菊花素:前列腺癌突变雄激素受体的潜在抗雄激素配体。
背景:雄激素受体突变,尤其是T877A和W741L,可促进前列腺癌(PCa)的发生。抗PCa的主要治疗方法是雄激素受体(AR)拮抗剂,包括比卡鲁胺;但这些药物会随着时间的推移而失去效力。黄菊花素是一种具有多种生物活性的类黄酮,包括抗肿瘤特性;然而,它作为抗雄激素的潜力必须加以探索。目的:本研究旨在表征和比较菊花素与野生型和突变型ARs的分子相互作用及其在体外PCa模型中的细胞毒作用。方法:采用分子对接的方法,比较比卡鲁胺和金菊素对野生型和突变型AR的亲和力和分子相互作用。MTT法评估了这些配体对DU-145 (T877A)和PC3 (W741L) PCa细胞系以及非肿瘤RWPE-1细胞的细胞毒性作用。结果:分子对接预测突变AR与野生型AR (WT-AR)有更高的亲合力;同时,比卡鲁胺对WT-AR具有较高的亲和力。这些受体结合位点内参与分子相互作用的氨基酸残基根据配体和AR变异而改变,影响它们的亲和力评分和生物效应(激动剂/拮抗剂)。菊花素对前列腺癌肿瘤细胞有特异性细胞毒作用,对非肿瘤细胞无特异性细胞毒作用。相比之下,比卡鲁胺对所有细胞系都显示出强大的细胞毒性。结论:本研究证明了黄菊花素对突变AR的潜在抗雄激素作用和对PCa细胞的特异性细胞毒性,提示黄菊花素可用于PCa治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信