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Mitochondrial Elongation and ROS-Mediated Apoptosis in Prostate Cancer Cells under Therapy with Apalutamide and Complex I Inhibitor.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Jun 25; Vol. 25 (13). Date of Electronic Publication: 2024 Jun 25. - Publication Year :
- 2024
-
Abstract
- Metabolic reprogramming and mitochondrial dynamics are pivotal in prostate cancer (PCa) progression and treatment resistance, making them essential targets for therapeutic intervention. In this study, we investigated the effects of the androgen receptor antagonist apalutamide (ARN) and the mitochondrial electron transport chain complex I inhibitor IACS-010759 (IACS) on the mitochondrial network architecture and dynamics in PCa cells. Treatment with ARN and/or IACS induced significant changes in mitochondrial morphology, particularly elongation, in androgen-sensitive PCa cells. Additionally, ARN and IACS modulated the mitochondrial fission and fusion processes, indicating a convergence of metabolic and androgen-signaling pathways in shaping mitochondrial function. Notably, the combination treatment with ARN and IACS resulted in increased apoptotic cell death and mitochondrial oxidative stress selectively in the androgen-sensitive PCa cells. Our findings highlight the therapeutic potential of targeting mitochondrial metabolism in prostate cancer and emphasize the need for further mechanistic understanding to optimize treatment strategies and improve patient outcomes.<br />Competing Interests: The authors declare no conflicts of interest.
- Subjects :
- Humans
Male
Cell Line, Tumor
Mitochondrial Dynamics drug effects
Oxidative Stress drug effects
Androgen Receptor Antagonists pharmacology
Androgen Receptor Antagonists therapeutic use
Mitochondria metabolism
Mitochondria drug effects
Prostatic Neoplasms metabolism
Prostatic Neoplasms drug therapy
Prostatic Neoplasms pathology
Apoptosis drug effects
Reactive Oxygen Species metabolism
Thiohydantoins pharmacology
Thiohydantoins therapeutic use
Electron Transport Complex I metabolism
Electron Transport Complex I antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39000047
- Full Text :
- https://doi.org/10.3390/ijms25136939