{"title":"环姜黄素能有效抑制人芳香化酶，是一种潜在的治疗药物。","authors":"Han Lu, Jingyi Zheng, Chunnan Hu, Jiayi He, Shaowei Wang, Zhuoqi Chen, Yiyan Wang, Huitao Li, Ren-Shan Ge, Yunbing Tang, Yingfen Ying","doi":"10.1016/j.jsbmb.2024.106672","DOIUrl":null,"url":null,"abstract":"<p><p>Curcuminoids, including curcumin and its derivatives, show potent inhibition of aromatase (CYP19A1), crucial for estradiol synthesis and breast cancer metastasis. Our study evaluated the efficacy and mechanism of 10 curcuminoids and their metabolites against human and rat CYP19A1 using placental microsomes, revealing species-specific IC<sub>50</sub> values. Cyclocurcumin (IC<sub>50</sub>, 4.43 μM) and curcumin (IC<sub>50</sub>, 3.49 μM) were the most effective inhibitors for human and rat CYP19A1, respectively. These compounds acted as mixed or competitive inhibitors, reducing estradiol production in human BeWo cells. Docking analysis showed that curcuminoids interact with CYP19A1 active site, forming a hydrogen bond with Met374. 3D-QSAR analysis highlighted the importance of hydrogen bonding in inhibition. A negative correlation was observed between the pKa values and IC<sub>50</sub> values for human CYP19A1. A positive correlation was observed between the lowest binding energy and IC<sub>50</sub> values for human CYP19A1. These findings underscore the potential of curcuminoids as therapeutic agents against breast cancer.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106672"},"PeriodicalIF":2.7000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cyclocurcumin potently inhibits human aromatase as a potential therapeutic agent.\",\"authors\":\"Han Lu, Jingyi Zheng, Chunnan Hu, Jiayi He, Shaowei Wang, Zhuoqi Chen, Yiyan Wang, Huitao Li, Ren-Shan Ge, Yunbing Tang, Yingfen Ying\",\"doi\":\"10.1016/j.jsbmb.2024.106672\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Curcuminoids, including curcumin and its derivatives, show potent inhibition of aromatase (CYP19A1), crucial for estradiol synthesis and breast cancer metastasis. Our study evaluated the efficacy and mechanism of 10 curcuminoids and their metabolites against human and rat CYP19A1 using placental microsomes, revealing species-specific IC<sub>50</sub> values. Cyclocurcumin (IC<sub>50</sub>, 4.43 μM) and curcumin (IC<sub>50</sub>, 3.49 μM) were the most effective inhibitors for human and rat CYP19A1, respectively. These compounds acted as mixed or competitive inhibitors, reducing estradiol production in human BeWo cells. Docking analysis showed that curcuminoids interact with CYP19A1 active site, forming a hydrogen bond with Met374. 3D-QSAR analysis highlighted the importance of hydrogen bonding in inhibition. A negative correlation was observed between the pKa values and IC<sub>50</sub> values for human CYP19A1. A positive correlation was observed between the lowest binding energy and IC<sub>50</sub> values for human CYP19A1. These findings underscore the potential of curcuminoids as therapeutic agents against breast cancer.</p>\",\"PeriodicalId\":51106,\"journal\":{\"name\":\"Journal of Steroid Biochemistry and Molecular Biology\",\"volume\":\" \",\"pages\":\"106672\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-12-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Steroid Biochemistry and Molecular Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jsbmb.2024.106672\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Steroid Biochemistry and Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jsbmb.2024.106672","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Cyclocurcumin potently inhibits human aromatase as a potential therapeutic agent.
Curcuminoids, including curcumin and its derivatives, show potent inhibition of aromatase (CYP19A1), crucial for estradiol synthesis and breast cancer metastasis. Our study evaluated the efficacy and mechanism of 10 curcuminoids and their metabolites against human and rat CYP19A1 using placental microsomes, revealing species-specific IC50 values. Cyclocurcumin (IC50, 4.43 μM) and curcumin (IC50, 3.49 μM) were the most effective inhibitors for human and rat CYP19A1, respectively. These compounds acted as mixed or competitive inhibitors, reducing estradiol production in human BeWo cells. Docking analysis showed that curcuminoids interact with CYP19A1 active site, forming a hydrogen bond with Met374. 3D-QSAR analysis highlighted the importance of hydrogen bonding in inhibition. A negative correlation was observed between the pKa values and IC50 values for human CYP19A1. A positive correlation was observed between the lowest binding energy and IC50 values for human CYP19A1. These findings underscore the potential of curcuminoids as therapeutic agents against breast cancer.
期刊介绍：
The Journal of Steroid Biochemistry and Molecular Biology is devoted to new experimental and theoretical developments in areas related to steroids including vitamin D, lipids and their metabolomics. The Journal publishes a variety of contributions, including original articles, general and focused reviews, and rapid communications (brief articles of particular interest and clear novelty). Selected cutting-edge topics will be addressed in Special Issues managed by Guest Editors. Special Issues will contain both commissioned reviews and original research papers to provide comprehensive coverage of specific topics, and all submissions will undergo rigorous peer-review prior to publication.
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