Pd03-06 Mitochondrial Complex I Protein Ndufs3 Is Decreased in Benign Prostatic Hyperplasia Patients Treated With Celecoxib and/or Finasteride

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology (PD03)1 May 2024PD03-06 MITOCHONDRIAL COMPLEX I PROTEIN NDUFS3 IS DECREASED IN BENIGN PROSTATIC HYPERPLASIA PATIENTS TREATED WITH CELECOXIB AND/OR FINASTERIDE Chandler N. Hudson, Teresa T. Liu, Taro Igarashi, Nathalie El-Khoury, Nnamdi Ihejirika, Kelsey Paxton, Juliann Jaumotte, Rajiv Dhir, Joel B. Nelson, Donald B. DeFranco, William A. Ricke, Naoki Yoshimura, Zhou Wang, and Laura E. Pascal Chandler N. HudsonChandler N. Hudson , Teresa T. LiuTeresa T. Liu , Taro IgarashiTaro Igarashi , Nathalie El-KhouryNathalie El-Khoury , Nnamdi IhejirikaNnamdi Ihejirika , Kelsey PaxtonKelsey Paxton , Juliann JaumotteJuliann Jaumotte , Rajiv DhirRajiv Dhir , Joel B. NelsonJoel B. Nelson , Donald B. DeFrancoDonald B. DeFranco , William A. RickeWilliam A. Ricke , Naoki YoshimuraNaoki Yoshimura , Zhou WangZhou Wang , and Laura E. PascalLaura E. Pascal View All Author Informationhttps://doi.org/10.1097/01.JU.0001009388.01015.e5.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is treated with multiple medical therapies and surgical options with variable outcomes. Some of the heterogeneity in treatment efficacy may come from an incomplete understanding of their molecular and cellular impact. A decline in essential mitochondrial protein expression has been observed in BPH tissues, suggesting mitochondrial dysfunction may be a factor in BPH pathogenesis. Both finasteride and celecoxib have been associated with mitochondrial toxicity in other tissues. The objective of this study was to determine whether the BPH therapies finasteride and celecoxib might impact mitochondrial function in prostate tissues, specifically their effects on NDUFS3. METHODS: NDUFS3, E-cadherin and inflammatory cell immunostaining were performed on simple prostatectomy BPH specimens from patients naïve to androgen manipulation who were treated with celecoxib and/or finasteride for 28 days in a four-arm, phase II randomized, single-blind clinical trial. NDUFS3 and inflammatory cell staining was also conducted in a murine model of celecoxib treatment in male mice. Quantification analyses of immunostaining were performed. RESULTS: NDUFS3 was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3, and however there was no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration. CONCLUSIONS: These findings suggest that celecoxib and/or finasteride are associated with a decline in NDUFS3 in prostate tissues but no change in inflammatory cell infiltration. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, therapeutic targeting of BPH with celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in BPH patients. Future development of therapeutic strategies improving mitochondrial function may improve the efficacy of celecoxib and/or finasteride in BPH patients. Source of Funding: This work was funded in part by NIH grants K01 AG059899 from NIA to TL; U54 DK104310, R01 DK131175, and R01 DK127081 from NIDDK to WAR; U54 DK112079 and R56 DK107492 from NIDDK to ZW; and CAIRIBU Convergence Award to LEP from NIDDK. This project also used the Pitt Biospecimen Core and was supported in part by award P30CA047904 © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e78 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Chandler N. Hudson More articles by this author Teresa T. Liu More articles by this author Taro Igarashi More articles by this author Nathalie El-Khoury More articles by this author Nnamdi Ihejirika More articles by this author Kelsey Paxton More articles by this author Juliann Jaumotte More articles by this author Rajiv Dhir More articles by this author Joel B. Nelson More articles by this author Donald B. DeFranco More articles by this author William A. Ricke More articles by this author Naoki Yoshimura More articles by this author Zhou Wang More articles by this author Laura E. Pascal More articles by this author Expand All Advertisement PDF downloadLoading ...