title: Psoralidin, a coumestan analogue, as a novel potent estrogen receptor signaling molecule isolated from Psoralea corylifolia.
abstract: A novel biological activity of psoralidin as an agonist for both estrogen receptor (ER)α and ERβ agonist has been demonstrated in our study. Psoralidin has been characterized as a full ER agonist, which activates the classical ER-signaling pathway in both ER-positive human breast and endometrial cell lines as well as non-human cultured cells transiently expressing either ERα or ERβ. The estrogenic activity was determined using the relative expression levels of either reporter or the endogenous genes dependent on the agonist-bound ER to the estrogen response element (ERE). Psoralidin at 10 μM was able to induce the maximum reporter gene expression corresponding to that of E2-treated cells and such activation of the ERE-reporter gene by psoralidin was completely abolished by the cotreatment of a pure ER antagonist, implying that the biological activities of psoralidin are mediated by ER. Psoralidin was also able to induce the endogenous estrogen-responsive gene, pS2, in human breast cancer cells MCF-7. It was observed that activation of the classical ER-signaling pathway by psoralidin is mediated via induction of ER conformation by psoralidin and direct binding of the psoralidin-ER complex to the EREs present in the promoter region of estrogen-responsive genes, as shown by chromatin immunoprecipitation assay results. Finally, molecular docking of psoralidin to the ligand binding pocket of the ERα showed that psoralidin is able to mimic the binding interactions of E2, and thus, it could act as an ER agonist in the cellular environment.
authors: Department of Biological Science, College of Science, Sookmyung Women's University, 47 Chungpa-ro, Yongsan-Gu, 140-742 Seoul, Republic of Korea.
authors: Xiyuan
authors: X
authors: Liu
authors: Graduate School of Pharmaceutical Sciences, Global Top5 Research Program, College of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, 120-750 Seoul, Republic of Korea.
authors: Joo-Won
authors: JW
authors: Nam
authors: College of Pharmacy, Sookmyung Women's University, 47 Chungpa-ro, Yongsan-Gu, 140-742 Seoul, Republic of Korea.
authors: Yun Seon
authors: YS
authors: Song
authors: Center for Neuro-Medicine, Korea Institute of Science and Technology, 136-791 Seoul, Republic of Korea; Department of Biological Chemistry, School of Science, University of Science and Technology, 52 Eoeun Dong, Yuseong-Gu, 305-333 Daejeon, Republic of Korea.
authors: Ambily Nath Indu
authors: AN
authors: Viswanath
authors: Center for Neuro-Medicine, Korea Institute of Science and Technology, 136-791 Seoul, Republic of Korea; Department of Biological Chemistry, School of Science, University of Science and Technology, 52 Eoeun Dong, Yuseong-Gu, 305-333 Daejeon, Republic of Korea.
authors: Ae Nim
authors: AN
authors: Pae
authors: Graduate School of Pharmaceutical Sciences, Global Top5 Research Program, College of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, 120-750 Seoul, Republic of Korea.
authors: Yun-Seo
authors: YS
authors: Kil
authors: College of Pharmacy, Sookmyung Women's University, 47 Chungpa-ro, Yongsan-Gu, 140-742 Seoul, Republic of Korea.
authors: Hee-Doo
authors: HD
authors: Kim
authors: Department of Biological Science, College of Science, Sookmyung Women's University, 47 Chungpa-ro, Yongsan-Gu, 140-742 Seoul, Republic of Korea.
authors: Jong Hoon
authors: JH
authors: Park
authors: Graduate School of Pharmaceutical Sciences, Global Top5 Research Program, College of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, 120-750 Seoul, Republic of Korea. Electronic address: yuny@ewha.ac.kr.
authors: Eun-Kyoung
authors: EK
authors: Seo
authors: Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University, 47 Chungpa-ro, Yongsan-Gu, 140-742 Seoul, Republic of Korea. Electronic address: minsunchang@sm.ac.kr.
authors: Minsun
authors: M
authors: Chang
mesh_terms: D001572:Benzofurans / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000378:metabolism; D005260:Female; D006801:Humans; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D029907:Psoralea / Q000737:chemistry* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001572:Benzofurans; D003374:Coumarins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen; C102768:psoralidin; C505898:coumestan
keywords: Estrogen receptor; Hormone replacement therapy; Phytoestrogen; Psoralea corylifolia; Psoralidin