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.

Základní údaje

Originální název

Nilotinib induces ER stress and cell death in H9c2 cells

Autoři

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

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30105 Physiology

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 1.461

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/16:00092559

Organizační jednotka

Lékařská fakulta

UT WoS

000392029200011

EID Scopus

2-s2.0-85009964006

Klíčová slova anglicky

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

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 4. 2017 12:34, Soňa Böhmová

Anotace

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.

Návaznosti

MUNI/A/1365/2015, interní kód MU

Název: Kardiovaskulární systém: od modelu přes terapii k prevenci (Akronym: KAMOTEPRE)

Investor: Masarykova univerzita, Kardiovaskulární systém: od modelu přes terapii k prevenci, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

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

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