The mechanism of cytotoxicity and DNA adduct formation by the anticancer drug ellipticine in human neuroblastoma cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F09%3A5287" target="_blank" >RIV/00064203:_____/09:5287 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/09:10001346 RIV/00216208:11130/09:5287

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

The mechanism of cytotoxicity and DNA adduct formation by the anticancer drug ellipticine in human neuroblastoma cells

Popis výsledku v původním jazyce

The mechanism of ellipticine action in human neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cell lines was investigated. Treatment of neuroblastoma with ellipticine resulted in apoptosis induction. This effect was associated with formation of covalent ellipticine-derived DNA adducts, identical to those formed by the cytochrome P450- and peroxidase-mediated ellipticine metabolites. The expression of these enzymes and their ability to generate ellipticine-DNA adducts in neuroblastoma were proven. The levelsof DNA adducts correlated with toxicity of ellipticine to IMR-32 and UKF-NB-4 cells, but not to UKF-NB-3. In addition, hypoxic conditions resulted in decrease in ellipticine toxicity and correlated with lower levels of adducts. Both these lines accumulated in S phase, suggesting that adducts interfere with DNA replication. The results demonstrate that among modes of ellipticine antitumor action, formation of adducts is the main mechanism of cytotoxicity to neuroblastoma.

Název v anglickém jazyce

The mechanism of cytotoxicity and DNA adduct formation by the anticancer drug ellipticine in human neuroblastoma cells

Popis výsledku anglicky

The mechanism of ellipticine action in human neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cell lines was investigated. Treatment of neuroblastoma with ellipticine resulted in apoptosis induction. This effect was associated with formation of covalent ellipticine-derived DNA adducts, identical to those formed by the cytochrome P450- and peroxidase-mediated ellipticine metabolites. The expression of these enzymes and their ability to generate ellipticine-DNA adducts in neuroblastoma were proven. The levelsof DNA adducts correlated with toxicity of ellipticine to IMR-32 and UKF-NB-4 cells, but not to UKF-NB-3. In addition, hypoxic conditions resulted in decrease in ellipticine toxicity and correlated with lower levels of adducts. Both these lines accumulated in S phase, suggesting that adducts interfere with DNA replication. The results demonstrate that among modes of ellipticine antitumor action, formation of adducts is the main mechanism of cytotoxicity to neuroblastoma.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2009

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Biochemical Pharmacology

ISSN

0006-2952

e-ISSN

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Svazek periodika

77

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

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Kód UT WoS článku

000265197000003

EID výsledku v databázi Scopus

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