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    Aldehyde Dehydrogenases and Prostate Cancer: Shedding Light on Isoform Distribution to Reveal Druggable Target

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    quattrini_et_al_2020.pdf (1.884Mb)
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    Publication date
    2020-12-04
    Author
    Quattrini, L.
    Sadiq, Maria
    Petrarolo, G.
    Maitland, N.J.
    Frame, F.M.
    Pors, Klaus
    La Motta, C.
    Keyword
    ALDH inhibitors
    ALDH1A1
    ALDH1A3
    Aldehyde dehydrogenase
    imidazo[1,2-a]pyridines
    Prostate cancer
    Rights
    (c) 2020 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/)
    Peer-Reviewed
    Yes
    
    Metadata
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    Abstract
    Prostate cancer represents the most common malignancy diagnosed in men, and is the second-leading cause of cancer death in this population. In spite of dedicated efforts, the current therapies are rarely curative, requiring the development of novel approaches based on innovative molecular targets. In this work, we validated aldehyde dehydrogenase 1A1 and 1A3 isoform expressions in different prostatic tissue-derived cell lines (normal, benign and malignant) and patient-derived primary prostate tumor epithelial cells, demonstrating their potential for therapeutic intervention using a small library of aldehyde dehydrogenase inhibitors. Compound 3b, 6-(4-fluorophenyl)-2-phenylimidazo [1,2-a]pyridine exhibited not only antiproliferative activity in the nanomolar range against the P4E6 cell line, derived from localized prostate cancer, and PC3 cell lines, derived from prostate cancer bone metastasis, but also inhibitory efficacy against PC3 colony-forming efficiency. Considering its concomitant reduced activity against normal prostate cells, 3b has the potential as a lead compound to treat prostate cancer by means of a still untapped molecular target.
    URI
    http://hdl.handle.net/10454/18249
    Version
    Published version
    Citation
    Quattrini L, Sadiq M, Petrarolo G et al (2020) Aldehyde Dehydrogenases and Prostate Cancer: Shedding Light on Isoform Distribution to Reveal Druggable Target. Biomedicines. 8(12): E569.
    Link to publisher’s version
    https://doi.org/10.3390/biomedicines8120569
    Type
    Article
    Collections
    Life Sciences Publications

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