Cyclocurcumin potently inhibits human aromatase as a potential therapeutic agent

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

Cyclocurcumin potently inhibits human aromatase as a potential therapeutic agent

J Steroid Biochem Mol Biol. 2024 Dec 31:247:106672. doi: 10.1016/j.jsbmb.2024.106672. Online ahead of print.

Authors

Han Lu¹, Jingyi Zheng², Chunnan Hu², Jiayi He², Shaowei Wang³, Zhuoqi Chen³, Yiyan Wang³, Huitao Li⁴, Ren-Shan Ge⁵, Yunbing Tang⁶, Yingfen Ying⁷

Affiliations

¹ Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Wenzhou Medical University, Zhejiang Province, China.
² Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Wenzhou Medical University, Zhejiang Province, China.
³ Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
⁴ Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
⁵ Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Environment and Male Reproductive Medicine of Wenzhou, Wenzhou Medical University, Zhejiang Province, China. Electronic address: [email protected].
⁶ Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: [email protected].
⁷ Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China. Electronic address: [email protected].

PMID: 39746524
DOI: 10.1016/j.jsbmb.2024.106672

Abstract

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.

Keywords: CYP19A1; Curcumin metabolites; Cyclocurcumin; Docking analysis; Inhibition.