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Fisetin induces apoptosis in uterine leiomyomas through multiple pathways
( Seul Ki Lee ),( Jisu Yeom ),( Min Hyung Jung ) 대한산부인과학회 2019 대한산부인과학회 학술대회 Vol.105 No.-
Objective: The aim of this work is to discover a potential natural agent that has pharmacological activities on uterine leiomyomas with fewer adverse effects. Methods: In this study, we investigated the potential of a natural medication, Rhus verniciflua Stokes (RVS), as a new therapeutic agent for leiomyomas. After primary cytotoxicity testing, we analyzed the RVS components that showed pharmacological activity. Leiomyoma cells and myometrium cells were cultured from uterine tissues obtained from patients, under the approval of the institutional review board of Kyung Hee University Hospital (IRB No. KUH 2017-11-064), and were treated with RVS at varying concentrations. Results: RVS was cytotoxic in both leiomyoma and myometrium cells; however, the effects were more prominent in the leiomyoma cells. Among the bioactive components of RVS, fisetin showed significant pharmacological effects on leiomyoma cells. Fisetin showed excellent leiomyoma cell cytotoxicity and induced apoptotic cell death with cell cycle arrest. The apoptotic cell death appeared to involve not one specific pathway but multichannel pathways (the intrinsic, extrinsic, MARK, and p53-mediated pathways), and autophagy. The multichannel apoptosis pathways were activated with a low dose of fisetin (< IC20) and were more vigorously activated at high doses ( > IC50). Conclusion: This is the first demonstration to show the pharmacological activities of fisetin on leiomyoma cells. These findings suggest that fisetin may be used for the prevention and treatment of uterine leiomyomas. Since fisetin can be obtained from plants, it may be a safe and effective alternative treatment for uterine leiomyomas.