ArticleThe Prostate2021
Prostate cancer cells survive anti-androgen and mitochondrial metabolic inhibitors by modulating glycolysis and mitochondrial metabolic activities.
Article in The Prostate, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 31 citations in OpenAlex.
- 70 Years of DON and Beyond: Glutaminase Inhibition as a Synergistic Strategy in Cancer Combination Therapy.Pharmaceutics · 2026Review
- OGDHL Promotes Prostate Cancer Progression and Regulates Neuroendocrine Marker Expression and Nucleotide Abundance.Molecular cancer research : MCR · 2026Article
- Androgen receptor signaling organizes ferroptosis escape in castration-resistant prostate cancer: a threshold-based model for therapeutic timing.Frontiers in oncology · 2026Review
- Mitochondrial convergence of ferroptosis and cuproptosis in castration-resistant prostate cancer: From metabolic vulnerabilities to therapeutic targeting.BBA advances · 2026Review
- OGDHL regulates tumor growth, neuroendocrine marker expression, and nucleotide abundance in prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Voluntary Exercise Attenuates Tumor Growth in a Preclinical Model of Castration-Resistant Prostate Cancer.Medicine and science in sports and exercise · 2025Article
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- Inhibition of Mitochondrial-Associated Protein MAGMAS Resensitizes Chemoresistant Prostate Cancer Cells to Docetaxel.Cancers · 2025Article
- Prostate cancer exploits BRD9-driven metabolic reprogramming to shape the aggressive phenotype.Cell death & disease · 2025Article
- PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- MED12 and CDK8/19 Modulate Androgen Receptor Activity and Enzalutamide Response in Prostate Cancer.Endocrinology · 2024Article
- The polyunsaturated fatty acid docosahexaenoic affects mitochondrial function in prostate cancer cells.Cancer & metabolism · 2024Article
- Enzalutamide Sensitizes Castration-Resistant Prostate Cancer to Copper-Mediated Cell Death.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Tracking down metabolic vulnerabilities inClinical and translational discovery · 2024Article
- Identification of prostate cancer bone metastasis related genes and potential therapy targets by bioinformatics and in vitro experiments.Journal of cellular and molecular medicine · 2024Article
- Targeting the fibroblast growth factor pathway in molecular subtypes of castration-resistant prostate cancer.The Prostate · 2024Article
- MYC is a regulator of androgen receptor inhibition-induced metabolic requirements in prostate cancer.Cell reports · 2023Article
- Mitoribosome sensitivity to HSP70 inhibition uncovers metabolic liabilities of castration-resistant prostate cancer.PNAS nexus · 2023Article
- Mitochondrial Alterations in Prostate Cancer: Roles in Pathobiology and Racial Disparities.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMost cancer cells are more glycolytic even under aerobic conditions compared with their normal counterparts. Recent evidence of tumor cell metabolism, however, shows that some tumors also increase mitochondrial oxidative phosphorylation (ox-phos) at some disease states during progression and/or development of drug resistance. Our data show that anti-androgen enzalutamide (ENZA) resistant prostate cancer (PCa) cells use more mitochondrial metabolism leading to higher ox-phos as compared to the ENZA-sensitive cells and can become vulnerable to mitochondrial metabolism targeted therapies.
methodsSeahorse assay, mass spectrometry and high resolution fluorescence confocal microscopy coupled with image analysis has been used to compare mitochondrial metabolism in ENZA-treated and -untreated anti-androgen-sensitive LNCaP and -resistant C4-2, CWR22ν1, and PCa2b cells. Ex vivo fluorescence microscopy and image analysis has been standardized to monitor mitochondrial electron transport (ETS) activity that likely increases ox-phos in circulating tumor cells (CTCs) isolated fom patients undergoing AR-targeted therapies.
resultsOur data show that PCa cells that are resistant to anti-androgen ENZA switch from glycolysis to ox-phos leading to an increased ETS activity. ENZA pretreated cells are more vulnerable to ETS component complex I inhibitor IACS-010759 (IACS) and mitochondrial glutaminase inhibitor CB-839 that reduces glutamate supply to tricarboxylic acid cycle. CTCs isolated from 6 of 20 patient blood samples showed relatively higher ETS activity than the rest of the patients. All six patients have developed ENZA resistance within less than 6 months of the sample collection.
conclusionThe enhanced growth inhibitory effects of mitochondrial metabolic inhibitors IACS and CB-839 in ENZA pretreated PCa cells provides a rationale for designing a drug combination trial. Patients can be selected for such trials by monitoring the mitochondrial ETS activities in their CTCs to maximize success.
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