Hydroxychloroquine modulates the progression of experimentally induced benign prostatic hyperplasia in rats via targeting EGFR/ERK/STAT3 and AR/FOXO1/TRAIL pathways: computational and in vivo studies
Rattachement africain : Égypte. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Benign prostatic hyperplasia (BPH) is a prevalent progressive age-related disorder in men, yet its etiopathophysiology remains poorly understood. Current treatments like finasteride (Fin) have limited long-term efficacy, necessitating alternative therapies. Hydroxychloroquine (HCQ), a safe antimalarial agent, possesses anti-inflammatory, immunomodulatory, and antiproliferative activities, however, its therapeutic effect in BPH has not been investigated. Accordingly, we examined its therapeutic potential and underlying mechanisms, alone or combined with Fin, in testosterone-induced BPH in rats. In BPH-induced rats, HCQ markedly reduced prostate weight and index, and PSA, testosterone, dihydrotestosterone, pro-inflammatory cytokines (TNF-α, κ and IL-6), and the transcription factor "NF-κB" levels, while improving histological abnormalities in epithelial and stromal tissues. HCQ reduced the mRNA expression of AR and ERK1/2, and decreased the protein levels of EGFR and STAT3. Additionally, HCQ increased the mRNA expression of FOXO1 and promoted apoptosis through both intrinsic and TRAIL-mediated pathways. This was evidenced by the upregulation of pro-apoptotic Bax and the downregulation of anti-apoptotic Bcl-2 and Bcl-XL levels in the intrinsic pathway, as well as the reduction in mRNA expression of DR4 and DR5 in the TRAIL-mediated pathway. Notably, combining HCQ with Fin enhanced these effects. Molecular docking revealed HCQ's strong interactions with androgen receptor (AR), EGFR, ERK1/2, FOXO, and TRAIL death receptors (DR4/DR5), comparable to Fin except for STAT3. Our findings suggest that HCQ modulates BPH progression by targeting STAT3/FOXO1/TRAIL and EGFR/ERK/AR pathways, offering a promising therapeutic strategy for BPH, either alone or in combination with Fin.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Hydroxychloroquine modulates the progression of experimentally induced benign prostatic hyperplasia in rats via targeting EGFR/ERK/STAT3 and AR/FOXO1/TRAIL pathways: computational and in vivo studies
- Date Crossref
- 20/06/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Theodor Bilharz Research Institute Pharmacology Department Giza, Égypte (code pays fourni par la source)Structure de recherche
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October University of Modern Sciences and Arts Égypte (code pays fourni par la source)Université ou école supérieure
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Cairo University National Cancer Institute Cairo University, Égypte (code pays fourni par la source)Université ou école supérieure
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New Giza University New Giza University, Égypte (code pays fourni par la source)Université ou école supérieure
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National Water Research Center Égypte (code pays fourni par la source)Structure de recherche
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Faculty of Pharmacy Department of Biochemistry Cairo, Égypte (pays nommé en fin d’affiliation)Université ou école supérieure
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School of Pharmacy Department of Biochemistry km 22 Cairo-Alexandria Desert Road, Égypte (pays nommé en fin d’affiliation)Université ou école supérieure
Pharmacology Department — Theodor Bilharz Research Institute (Giza, Égypte), October University of Modern Sciences and Arts (Égypte) et National Cancer Institute — Cairo University (Cairo University, Égypte), avec 4 autres affiliations. Pays d’affiliation : Égypte.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.