Nilotinib induces ER stress and cell death in H9c2 cells

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Authors

LEKEŠ Denis SZADVÁRI Ivan KRIŽANOVÁ Oľga LOPUSNA K. REZUCHOVA I. NOVÁKOVÁ Marie NOVÁKOVÁ Zuzana PARAK T. BABULA Petr

Year of publication 2016
Type Article in Periodical
Magazine / Source Physiological Research
MU Faculty or unit

Faculty of Medicine

Citation
Field Physiology
Keywords Apoptosis; Cardiotoxicity; ER stress; Nilotinib; Reactive oxygen species
Description Tyrosine kinases inhibitors (TKi) represent a relatively novel class of anticancer drugs that target cellular pathways overexpressed in certain types of malignancies, such as chronic myeloid leukaemia (CML). Nilotinib, ponatinib and imatinib exhibit cardiotoxic and vascular effects. In this study, we focused on possible cardiotoxicity of nilotinib using H9C2 ceils as a suitable cell model. We studied rote of endoplasmic reticulum (ER) stress and apoptosis in nilotinib toxicity using a complex approach. Nilotinib impaired mitochondrial function and Induced formation of ROS under clinically relevant concentrations. In addition, ability of nilotinib to induce ER stress has been shown. These events result in apoptotic cell death. All these mechanisms contribute to cytotoxic effect of the drug. In addition, involvement of ER stress in niiotlnib toxicity may be important in co-treatment with Pharmaceuticals affecting ER and ER stress, e.g. beta-blockers or sartans, and should be further investigated.
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