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    NADH autofluorescence, a new metabolic biomarker for cancer stem cells: identification of vitamin C and CAPE as natural products targeting "stemness".

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    Authors
    Bonuccelli, Gloria
    De Francesco, Ernestina M
    de Boer, Rianne
    Tanowitz, Herbert B
    Lisanti, Michael P
    Affiliation
    The Paterson Building, University of Manchester, Withington, United Kingdom
    Issue Date
    2017-02-16
    
    Metadata
    Show full item record
    Abstract
    Here, we assembled a broad molecular "tool-kit" to interrogate the role of metabolic heterogeneity in the propagation of cancer stem-like cells (CSCs). First, we subjected MCF7 cells to "metabolic fractionation" by flow cytometry, using fluorescent mitochondrial probes to detect PCG1α activity, as well ROS and hydrogen-peroxide (H2O2) production; NADH levels were also monitored by auto-fluorescence. Then, the various cell populations were functionally assessed for "stem cell activity", using the mammosphere assay (3D-spheroids). Our results indicate that a sub-population of MCF7 cells, with increased PGC1α activity, high mitochondrial ROS/H2O2 production and high NADH levels, all form mammospheres with a higher efficiency. Thus, it appears that mitochondrial oxidative stress and the anti-oxidant response both contribute to the promotion of mitochondrial biogenesis and oxidative metabolism in CSCs. Further validation was provided by using specific inhibitors to target metabolic processes (the NAD+ salvage pathway, glycolysis, mitochondrial protein synthesis and OXPHOS), significantly reducing CSC propagation. As a consequence, we have now identified a variety of clinically-approved drugs (stiripentol), natural products (caffeic acid phenyl ester (CAPE), ascorbic acid, silibinin) and experimental pharmaceuticals (actinonin, FK866, 2-DG), that can be used to effectively inhibit CSC activity. We discuss the use of CAPE (derived from honey-bee propolis) and Vitamin C, as potential natural therapeutic modalities. In this context, Vitamin C was ~10 times more potent than 2-DG for the targeting of CSCs. Similarly, stiripentol was between 50 to 100 times more potent than 2-DG.
    Citation
    NADH autofluorescence, a new metabolic biomarker for cancer stem cells: identification of vitamin C and CAPE as natural products targeting "stemness". 2017, Oncotarget
    Journal
    Oncotarget
    URI
    http://hdl.handle.net/10541/620201
    DOI
    10.18632/oncotarget.15400
    PubMed ID
    28223550
    Type
    Article
    Language
    en
    ISSN
    1949-2553
    ae974a485f413a2113503eed53cd6c53
    10.18632/oncotarget.15400
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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