Chemical screening identifies the β-Carboline alkaloid harmine to be synergistically lethal with doxorubicin.

Autor: Atteya R; Center of Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt., Ashour ME; Center of Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt., Ibrahim EE; Center of Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt., Farag MA; Deparrtment of Pharamcognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., El-Khamisy SF; Center of Genomics, Helmy Institute for Medical Sciences, Zewail City of Science and Technology, Giza, Egypt; Krebs Institute, University of Sheffield, Sheffield, S10 2TN, UK. Electronic address: s.el-khamisy@sheffield.ac.uk.
Jazyk: angličtina
Zdroj: Mechanisms of ageing and development [Mech Ageing Dev] 2017 Jan; Vol. 161 (Pt A), pp. 141-148. Date of Electronic Publication: 2016 Jun 06.
DOI: 10.1016/j.mad.2016.04.012
Abstrakt: 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.
(Copyright © 2016 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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