Redukce doxorubicinu a oracinu a indukce karbonyl reduktázy v lidských prsních nádorových buňkách MCF-7

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F08%3A%230000461" target="_blank" >RIV/00027162:_____/08:#0000461 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/08:00109170

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Reduction of doxorubicin and oracin and induction of carbonyl reductase in human breast carcinoma MCF-7 cells

Popis výsledku v původním jazyce

In cancer cells, the drug-metabolizing enzymes may deactivate cytostatics, thus contributing to their survival. We found that MCF-7 cells were able to effectively metabolize both DOX and ORC through reduction of their carbonyl groups. The reduction of ORC was stereospecific, with a preferential formation of (+) enantiomer of dihydrooracin (DHO). The cytosolic carbonyl reductase CBR1 seemed to be a principal enzyme reducing both drugs, while cytosolic aldo-keto reductase AKR1C3 or microsomal reductases probably did not play important role in metabolism of either DOX or ORC. The exposure of MCF-7 cells to low (nanomolar) concentrations of DOX or ORC caused a significant elevation of reduction rates of both cytostatics, accompanied with an increase of CBR1 protein levels. Taken together, the present results seem to suggest that the accelerated metabolic deactivation of ORC or DOX might contribute to the survival of breast cancer cells during exposure to these cytostatics.

Název v anglickém jazyce

Reduction of doxorubicin and oracin and induction of carbonyl reductase in human breast carcinoma MCF-7 cells

Popis výsledku anglicky

In cancer cells, the drug-metabolizing enzymes may deactivate cytostatics, thus contributing to their survival. We found that MCF-7 cells were able to effectively metabolize both DOX and ORC through reduction of their carbonyl groups. The reduction of ORC was stereospecific, with a preferential formation of (+) enantiomer of dihydrooracin (DHO). The cytosolic carbonyl reductase CBR1 seemed to be a principal enzyme reducing both drugs, while cytosolic aldo-keto reductase AKR1C3 or microsomal reductases probably did not play important role in metabolism of either DOX or ORC. The exposure of MCF-7 cells to low (nanomolar) concentrations of DOX or ORC caused a significant elevation of reduction rates of both cytostatics, accompanied with an increase of CBR1 protein levels. Taken together, the present results seem to suggest that the accelerated metabolic deactivation of ORC or DOX might contribute to the survival of breast cancer cells during exposure to these cytostatics.

Druh

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

CEP obor

DN - Vliv životního prostředí na zdraví

OECD FORD obor

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Projekt

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Návaznosti

Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2008

Kód důvěrnosti údajů

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

Název periodika

Chemico-biological Interactions

ISSN

0009-2797

e-ISSN

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Svazek periodika

176

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

9

Strana od-do

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Kód UT WoS článku

000260664500002

EID výsledku v databázi Scopus

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