Nilotinib induces ER stress and cell death in H9c2 cells

J 2016

Nilotinib induces ER stress and cell death in H9c2 cells

LEKEŠ, Denis, Ivan SZADVÁRI, Oľga KRIŽANOVÁ, K. LOPUSNA, I. REZUCHOVA et. al.

Basic information

Original name

Nilotinib induces ER stress and cell death in H9c2 cells

Authors

LEKEŠ, Denis (703 Slovakia, belonging to the institution), Ivan SZADVÁRI (703 Slovakia, belonging to the institution), Oľga KRIŽANOVÁ (703 Slovakia, belonging to the institution), K. LOPUSNA (703 Slovakia), I. REZUCHOVA (703 Slovakia), Marie NOVÁKOVÁ (203 Czech Republic, belonging to the institution), Zuzana NOVÁKOVÁ (203 Czech Republic, belonging to the institution), T. PARAK (203 Czech Republic) and Petr BABULA (203 Czech Republic, guarantor, belonging to the institution)

Edition

Physiological Research, Praha, Fyziologický ústav AV ČR, 2016, 0862-8408

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 1.461

RIV identification code

RIV/00216224:14110/16:00092559

Organization unit

Faculty of Medicine

UT WoS

000392029200011

Keywords in English

Apoptosis; Cardiotoxicity; ER stress; Nilotinib; Reactive oxygen species

Abstract

V originále

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.

Links

MUNI/A/1365/2015, interní kód MU

Name: Kardiovaskulární systém: od modelu přes terapii k prevenci (Acronym: KAMOTEPRE)

Investor: Masaryk University, Category A

Citovat

LEKEŠ, Denis, Ivan SZADVÁRI, Oľga KRIŽANOVÁ, K. LOPUSNA, I. REZUCHOVA, Marie NOVÁKOVÁ, Zuzana NOVÁKOVÁ, T. PARAK and Petr BABULA. Nilotinib induces ER stress and cell death in H9c2 cells. Physiological Research. Praha: Fyziologický ústav AV ČR, 2016, vol. 65, Suppl. 4, p. "S505"-"S514", 10 pp. ISSN 0862-8408.

@article{1366115,
   author = {Lekeš, Denis and Szadvári, Ivan and Križanová, Oľga and Lopusna, K. and Rezuchova, I. and Nováková, Marie and Nováková, Zuzana and Parak, T. and Babula, Petr},
   article_location = {Praha},
   article_number = {Suppl. 4},
   keywords = {Apoptosis; Cardiotoxicity; ER stress; Nilotinib; Reactive oxygen species},
   language = {eng},
   issn = {0862-8408},
   journal = {Physiological Research},
   title = {Nilotinib induces ER stress and cell death in H9c2 cells},
   volume = {65},
   year = {2016}
}

TY  - JOUR
ID  - 1366115
AU  - Lekeš, Denis - Szadvári, Ivan - Križanová, Oľga - Lopusna, K. - Rezuchova, I. - Nováková, Marie - Nováková, Zuzana - Parak, T. - Babula, Petr
PY  - 2016
TI  - Nilotinib induces ER stress and cell death in H9c2 cells
JF  - Physiological Research
VL  - 65
IS  - Suppl. 4
SP  - "S505"-"S514"
EP  - "S505"-"S514"
PB  - Fyziologický ústav AV ČR
SN  - 08628408
KW  - Apoptosis
KW  - Cardiotoxicity
KW  - ER stress
KW  - Nilotinib
KW  - Reactive oxygen species
N2  - 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.
ER  -

LEKEŠ, Denis, Ivan SZADVÁRI, Oľga KRIŽANOVÁ, K. LOPUSNA, I. REZUCHOVA, Marie NOVÁKOVÁ, Zuzana NOVÁKOVÁ, T. PARAK and Petr BABULA. Nilotinib induces ER stress and cell death in H9c2 cells. \textit{Physiological Research}. Praha: Fyziologický ústav AV ČR, 2016, vol.~65, Suppl. 4, p.~''S505''-''S514'', 10 pp. ISSN~0862-8408.

Detailed Information on Publication Record