ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1661201
This article is part of the Research TopicNovel Therapeutics for Urological CancersView all 7 articles
Nobiletin mitigates benign prostatic hyperplasia by suppressing prostate cell proliferation through regulation of cell cycle progression, signaling pathways, transcription factor activity, and the androgen-signaling axis
Provisionally accepted
Jun-Hui Song1Daeun Lee1Byungdoo Hwang1Seon-Kyung Hwang1Sumin Choo1Hyeon Ji Jeong2Hoon Kim3Seok-Joong Yun2
Yung Hyun Choi4Wun-Jae Kim2
Sung-Kwon Moon1*- 1Chung-Ang University, Seoul, Republic of Korea
- 2Chungbuk National University, Cheongju-si, Republic of Korea
- 3Anyang University, Anyang-si, Republic of Korea
- 4Dong-Eui University, Busan, Republic of Korea
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Background and aim: Benign prostatic hyperplasia (BPH) involves androgen-driven proliferation with reduced apoptosis. Current 5α-reductase inhibitors can cause adverse effects, motivating safer options. We evaluated whether nobiletin, a polymethoxyflavonoid, mitigates BPH features. Methodology: In vitro, nobiletin was applied to BPH-1 epithelial and WPMY-1 stromal cells to assess anti-proliferative effects. In vivo efficacy was tested in a testosterone-induced BPH rat model administered oral nobiletin (1 or 5 mg/kg). Results: Nobiletin induced G0/G1 phase cell cycle arrest by suppressing cyclin D1, cyclin E, and cyclin-dependent kinase 2 (CDK2), while elevating p21 and p27 expression. Expression of 5α-reductase, androgen receptor (AR), fibroblast growth factor (FGF), epidermal growth factor (EGF), and B-cell lymphoma 2 (Bcl-2) was reduced, whereas Bcl-2–associated X protein (Bax) was increased. Nobiletin modulated phosphorylation of c-Jun N-terminal kinase (JNK) and p38 and suppression of protein kinase B (AKT) phosphorylation. Nobiletin reduced nuclear factor kappa B (NF-κB) DNA-binding activity, which was dependent on JNK and p38. In vivo, nobiletin reduced prostate size, weight, and epithelial thickness, accompanied by molecular markers changing in the same direction as in vitro. Molecular docking analysis further supported the potential of nobiletin to bind 5α-reductase type 2 at the catalytic site. Conclusion: These results highlight the potential of nobiletin as a novel therapeutic option for BPH.
Keywords: Benign prostatic hyperplasia, Nobiletin, Cell Cycle, 5α-Reductase, NF-κB
Received: 16 Jul 2025; Accepted: 21 Oct 2025.
Copyright: © 2025 Song, Lee, Hwang, Hwang, Choo, Jeong, Kim, Yun, Choi, Kim and Moon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sung-Kwon Moon, sumoon66@cau.ac.kr
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