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Umbelliferone Ameliorates Benign Prostatic Hyperplasia by Inhibiting Cell Proliferation and G1/S Phase Cell Cycle Progression through Regulation of STAT3/E2F1 Axis.

Abstract
Umbelliferone (UMB), also known as 7-hydroxycoumarin, is a derivative of coumarin, which is widely found in many plants such as carrots, coriander, and garden angelica. Although many studies have already revealed the various pharmacological properties of UMB, its effect on benign prostatic hyperplasia (BPH) remains unclear. Therefore, the present study aimed to elucidate the underlying mechanism of the anti-proliferative effect of UMB in a human benign prostatic hyperplasia cell line (BPH-1), as well as its ameliorative effect on BPH in testosterone propionate (TP)-induced rats. The results showed that UMB exerts an anti-proliferative effect in BPH-1 cells by modulating the signal transducer and activator of transcription 3 (STAT3)/E2F transcription factor 1 (E2F1) axis. UMB treatment not only inhibited androgen/androgen receptor (AR) signaling-related markers, but also downregulated the overexpression of G1/S phase cell cycle-related markers. In TP-induced rats, UMB administration demonstrated an anti-BPH effect by significantly reducing prostate size, weight, and epithelial thickness. In addition, UMB suppressed cell proliferation by reducing the expression of proliferating cell nuclear antigen (PCNA) and p-STAT3 (Tyr 705) in prostate tissue following TP injection. These findings suggest that UMB has pharmacological effects against BPH.
AuthorsHyo-Jung Kim, Bo-Ram Jin, Hyo-Jin An
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 16 (Aug 21 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID34445725 (Publication Type: Journal Article)
Chemical References
  • Receptors, Androgen
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Umbelliferones
  • 7-hydroxycoumarin
  • Testosterone Propionate
Topics
  • Animals
  • Cell Cycle (drug effects)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Drug Evaluation, Preclinical
  • Male
  • Prostate (drug effects, pathology)
  • Prostatic Hyperplasia (drug therapy, metabolism, pathology)
  • Rats, Wistar
  • Receptors, Androgen (metabolism)
  • STAT3 Transcription Factor (metabolism)
  • Testosterone Propionate
  • Transforming Growth Factor beta1 (metabolism)
  • Umbelliferones (pharmacology, therapeutic use)

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