کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5503735 1535594 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Chemical screening identifies the β-Carboline alkaloid harmine to be synergistically lethal with doxorubicin
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Chemical screening identifies the β-Carboline alkaloid harmine to be synergistically lethal with doxorubicin
چکیده انگلیسی


- Synergistic cytotoxicity of harmine and doxorubicin on MCF-7 breast cancer cells.
- Harmine does not enhance the cytotoxicity of Etoposide or Camptothecin.
- Doxorubicin and harmine combination could reduce doxorubicin's cardiotoxicity.

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mechanisms of Ageing and Development - Volume 161, Part A, January 2017, Pages 141-148
نویسندگان
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