دورية أكاديمية
أعرض في EDS

Investigation of Mitochondrial Metabolic Response to Doxorubicin in Prostate Cancer Cells: An NADH, FAD and Tryptophan FLIM Assay.

التفاصيل البيبلوغرافية
العنوان: Investigation of Mitochondrial Metabolic Response to Doxorubicin in Prostate Cancer Cells: An NADH, FAD and Tryptophan FLIM Assay.
المؤلفون: Alam SR; The W.M. Keck Center for Cellular Imaging, Physical and Life Sciences Building, University of Virginia, 90 Geldard Dr., Charlottesville, Virginia, 22904, USA., Wallrabe H; The W.M. Keck Center for Cellular Imaging, Physical and Life Sciences Building, University of Virginia, 90 Geldard Dr., Charlottesville, Virginia, 22904, USA., Svindrych Z; The W.M. Keck Center for Cellular Imaging, Physical and Life Sciences Building, University of Virginia, 90 Geldard Dr., Charlottesville, Virginia, 22904, USA., Chaudhary AK; Roswell Park Cancer Institute, Centre for Genetics and Pharmacology, Department of Pharmacology and Therapeutics, Elm & Carlton Streets, Buffalo, New York, 14263, USA., Christopher KG; Departments of Biology and Biomedical Engineering, University of Virginia, 90 Geldard Dr., Charlottesville, Virginia, 22904, USA., Chandra D; Roswell Park Cancer Institute, Centre for Genetics and Pharmacology, Department of Pharmacology and Therapeutics, Elm & Carlton Streets, Buffalo, New York, 14263, USA., Periasamy A; The W.M. Keck Center for Cellular Imaging, Physical and Life Sciences Building, University of Virginia, 90 Geldard Dr., Charlottesville, Virginia, 22904, USA. ap3t@virginia.edu.; Departments of Biology and Biomedical Engineering, University of Virginia, 90 Geldard Dr., Charlottesville, Virginia, 22904, USA. ap3t@virginia.edu.
المصدر: Scientific reports [Sci Rep] 2017 Sep 05; Vol. 7 (1), pp. 10451. Date of Electronic Publication: 2017 Sep 05.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Antibiotics, Antineoplastic/*pharmacology , Doxorubicin/*pharmacology , Energy Metabolism/*drug effects , Mitochondria/*drug effects , Mitochondria/*metabolism , Prostatic Neoplasms/*metabolism, Apoptosis/drug effects ; Cell Line, Tumor ; Flavin-Adenine Dinucleotide/metabolism ; Humans ; Male ; Microscopy, Fluorescence ; NADP/metabolism ; Optical Imaging ; Oxidation-Reduction ; Oxidative Phosphorylation/drug effects ; Oxidative Stress ; Reactive Oxygen Species ; Tryptophan/metabolism
مستخلص: Prostate cancer (PCa) is one of the leading cancers in men in the USA. Lack of experimental tools that predict therapy response is one of the limitations of current therapeutic regimens. Mitochondrial dysfunctions including defective oxidative phosphorylation (OXPHOS) in cancer inhibit apoptosis by modulating ROS production and cellular signaling. Thus, correction of mitochondrial dysfunction and induction of apoptosis are promising strategies in cancer treatment. We have used Fluorescence Lifetime Imaging Microscopy (FLIM) to quantify mitochondrial metabolic response in PCa cells by tracking auto-fluorescent NAD(P)H, FAD and tryptophan (Trp) lifetimes and their enzyme-bound fractions as markers, before and after treatment with anti-cancer drug doxorubicin. A 3-channel FLIM assay and quantitative analysis of these markers for cellular metabolism show in response to doxorubicin, NAD(P)H mean fluorescence lifetime (τ m ) and enzyme-bound (a 2 %) fraction increased, FAD enzyme-bound (a 1 %) fraction was decreased, NAD(P)H-a 2 %/FAD-a 1 % FLIM-based redox ratio and ROS increased, followed by induction of apoptosis. For the first time, a FRET assay in PCa cells shows Trp-quenching due to Trp-NAD(P)H interactions, correlating energy transfer efficiencies (E%) vs NAD(P)H-a 2 %/FAD-a 1 % as sensitive parameters in predicting drug response. Applying this FLIM assay as early predictor of drug response would meet one of the important goals in cancer treatment.
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معلومات مُعتمدة: R21 EB020843 United States EB NIBIB NIH HHS; S10 OD016446 United States OD NIH HHS
المشرفين على المادة: 0 (Antibiotics, Antineoplastic)
0 (Reactive Oxygen Species)
146-14-5 (Flavin-Adenine Dinucleotide)
53-59-8 (NADP)
80168379AG (Doxorubicin)
8DUH1N11BX (Tryptophan)
تواريخ الأحداث: Date Created: 20170907 Date Completed: 20190509 Latest Revision: 20190509
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC5585313
DOI: 10.1038/s41598-017-10856-3
PMID: 28874842
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-017-10856-3