Fisetin induces apoptosis in uterine leiomyomas through multiple pathways

Jin-Woo Lee, Hyuck Choi, Eun‐jin Kim, Woo Yeon Hwang, Min Hyung Jung, Kyung Sook Kim
In: Scientific Reports · 2020 · vol. 10(1) , pp. 7993 · doi:10.1038/s41598-020-64871-y · PMID:32409692 · W3024223854
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⚙ AI-generated summary by claude@2026-06, 2026-06-10 ⓘ

Fisetin, a component of Rhus verniciflua Stokes, effectively induces apoptosis in uterine leiomyoma cells through intrinsic, extrinsic, MARK, and p53-mediated pathways, along with autophagy.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

This study evaluated whether the herbal extract Rhus verniciflua Stokes (RVS) and its components have pharmacological activity against uterine leiomyoma cells, using patient-derived cultured leiomyoma cells and normal myometrium cells treated with RVS at various concentrations. RVS was cytotoxic to both cell types, but fisetin showed the most pronounced effects on leiomyoma cells, inducing apoptotic cell death accompanied by cell-cycle arrest, with apoptosis-related pathways involving intrinsic, extrinsic, MAPK, and p53-mediated signaling plus autophagy. A key limitation the authors note is that RVS effects on myometrium and apoptosis in myometrium became more evident at higher concentrations, which they describe as harsher experimental conditions with less clear clinical relevance; they consider lower concentrations more meaningful. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Abstract Although uterine leiomyomas are the most common benign uterine tumors in women, there is no effective therapy that can also preserve the uterus and maintain fertility. The work aimed to work was to discover a potential natural agent that has pharmacological activities on uterine leiomyomas with fewer adverse effects. We chose Rhus verniciflua Stokes (RVS) as a candidate after primary cytotoxicity testing, and analyzed the RVS components that showed pharmacological activity. Leiomyoma cells and myometrium cells were cultured from uterine tissues obtained from patients, and were treated with RVS at varying concentrations. 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 (intrinsic, extrinsic, MARK, and p53-mediated pathways), and autophagy. The multichannel apoptosis pathways were activated with a low concentration of fisetin (IC 50 ). 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.

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