Atteya, R., Ashour, M.E., Ibrahim, E.E. et al. (2 more authors) (2017) Chemical screening identifies the β-Carboline alkaloid harmine to be synergistically lethal with doxorubicin. Mechanisms of Ageing and Development, 161 (A). pp. 141-148. ISSN 0047-6374
Abstract
Despite being an invaluable chemotherapeutic agent for several types of cancer, the clinical utility of doxorubicin is hampered by its age-related and dose-dependent cardiotoxicity. Co-administration of dexrazoxane as a cardioprotective agent has been proposed, however recent studies suggest that it attenuates doxorubicin-induced antitumor activity. Since compounds of natural origin present a rich territory for drug discovery, we set out to identify putative natural compounds with the view to mitigate or minimize doxorubicin cardiotoxicity. We identify the DYRK1A kinase inhibitor harmine, which phosphorylates Tau that is deregulated in Alzheimer's disease, as a potentiator of cell death induced by non-toxic doses of doxorubicin. These observations suggest that harmine or other compounds that target the DYRK1A kinase my offer a new therapeutic opportunity to suppress doxorubicin age-related and dose-dependent cardiotoxicity.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The Author(s). Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | Cardiotoxicity; DYRK1A kinase; Doxorubicin; Harmine; Natural products; TOP2 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Funding Information: | Funder Grant number BRITISH COUNCIL (THE) 171964603 LISTER INSTITUTE OF PREVENTATIVE MEDICINE NONE WELLCOME TRUST (THE) 103844/Z/14/Z |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Jul 2016 12:01 |
Last Modified: | 28 Jun 2017 13:58 |
Published Version: | http://dx.doi.org/10.1016/j.mad.2016.04.012 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.mad.2016.04.012 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101548 |