دورية أكاديمية
أعرض في EDS

Prostate cancer cells survive anti-androgen and mitochondrial metabolic inhibitors by modulating glycolysis and mitochondrial metabolic activities.

التفاصيل البيبلوغرافية
العنوان: Prostate cancer cells survive anti-androgen and mitochondrial metabolic inhibitors by modulating glycolysis and mitochondrial metabolic activities.
المؤلفون: Basu HS; Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Wilganowski N; Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Robertson S; Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Reuben JM; Department of Hematopathology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Cohen EN; Department of Hematopathology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Zurita A; Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Ramachandran S; Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Xiao LC; Department of Biostatistics, University of Texas, MD Anderson Cancer Center, Houston, Texas, USA., Titus M; Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA., Wilding G; Department of Genitourinary Oncology, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA.
المصدر: The Prostate [Prostate] 2021 Sep; Vol. 81 (12), pp. 799-811. Date of Electronic Publication: 2021 Jun 25.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Wiley-Liss Country of Publication: United States NLM ID: 8101368 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0045 (Electronic) Linking ISSN: 02704137 NLM ISO Abbreviation: Prostate Subsets: MEDLINE
أسماء مطبوعة: Publication: <2005-> : Hoboken, NJ : Wiley-Liss
Original Publication: New York : Alan R. Liss, c1980-
مواضيع طبية MeSH: Androgen Antagonists/*pharmacology , Antineoplastic Agents/*pharmacology , Benzamides/*pharmacology , Glycolysis/*physiology , Mitochondria/*metabolism , Nitriles/*pharmacology , Phenylthiohydantoin/*pharmacology , Prostatic Neoplasms, Castration-Resistant/*metabolism, Androgen Antagonists/therapeutic use ; Antineoplastic Agents/therapeutic use ; Benzamides/therapeutic use ; Benzeneacetamides/pharmacology ; Benzeneacetamides/therapeutic use ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell Survival/physiology ; Glycolysis/drug effects ; Humans ; Male ; Mitochondria/drug effects ; Nitriles/therapeutic use ; Phenylthiohydantoin/therapeutic use ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Thiadiazoles/pharmacology ; Thiadiazoles/therapeutic use
مستخلص: Background: Most 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.
Methods: Seahorse 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.
Results: Our 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.
Conclusion: The 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.
(© 2021 Wiley Periodicals LLC.)
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معلومات مُعتمدة: R01 CA185251 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Androgen Antagonists)
0 (Antineoplastic Agents)
0 (Benzamides)
0 (Benzeneacetamides)
0 (CB-839)
0 (Nitriles)
0 (Thiadiazoles)
2010-15-3 (Phenylthiohydantoin)
93T0T9GKNU (enzalutamide)
تواريخ الأحداث: Date Created: 20210625 Date Completed: 20220215 Latest Revision: 20240309
رمز التحديث: 20240309
مُعرف محوري في PubMed: PMC10921976
DOI: 10.1002/pros.24146
PMID: 34170017
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-0045
DOI:10.1002/pros.24146