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Fisetin induces apoptosis in uterine leiomyomas through multiple pathways.

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 (20) and were more vigorously activated at high concentrations (>IC₅₀). 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.

SUBMITTER: Lee JW

PROVIDER: S-EPMC7224361 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Fisetin induces apoptosis in uterine leiomyomas through multiple pathways.

Lee Jin-Woo JW Choi Hyuck Jai HJ Kim Eun-Jin EJ Hwang Woo Yeon WY Jung Min-Hyung MH Kim Kyung Sook KS

Scientific reports 20200514 1

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 m ...[more]

PMID: 32409692

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Project description:BackgroundUterine leiomyomas and adenomyosis are both common and often associated with abnormal uterine bleeding (AUB), including the symptom of heavy menstrual bleeding (HMB). Understanding the prevalence of adenomyosis in women with uterine leiomyomas could inform clinicians and patients in a way that may improve therapeutic approaches.ObjectiveTo explore the prevalence of adenomyosis in a group of women who underwent hysterectomy for AUB-L, to determine the prevalence of submucous leiomyomas, and to examine the utility of preoperative ultrasound to detect the presence of adenomyosis.MethodsThe Kaiser Permanente Hysterectomy Database (KPHD) was searched for women aged 18-52 undergoing hysterectomy for leiomyoma-associated chronic AUB (AUB-L) in 2018 and 2019. A target sample of 400 comprised those with at least 3 years in the Health System. Radiologists evaluated preoperative pelvic ultrasound images to determine leiomyoma size and level 2 FIGO type (submucous or other), and the linked electronic medical record abstracted for clinical features, including histopathological evidence of adenomyosis.ResultsOf the 370 subjects that met the study criteria, adenomyosis was identified via histopathology in 170 (45.9%). There was no difference in the adenomyosis prevalence with (47.1%) and without (43.0%) at least one submucous leiomyoma. Subgroup analysis of ultrasound images by an expert radiologist for the presence of adenomyosis demonstrated a positive predictive value of 54.0% and a negative predictive value of 43.4%.ConclusionsAdenomyosis was present in almost half of this AUB-L cohort undergoing hysterectomy and was equally prevalent in those with and without submucous leiomyomas as determined by sonographic evaluation. The imaging findings are in accord with prior investigators and demonstrate that 2-D ultrasound is insensitive to the presence of adenomyosis when the uterus is affected by leiomyomas. Further research is necessary to determine the impact of various adenomyosis phenotypes on the presence and severity of the symptom of HMB.

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Fisetin induces apoptosis in uterine leiomyomas through multiple pathways.

Publications

Fisetin induces apoptosis in uterine leiomyomas through multiple pathways.

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