VPA does not enhance platinum binding to DNA in cisplatin-resistant neuroblastoma cancer cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F17%3A10369466" target="_blank" >RIV/00064203:_____/17:10369466 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/17:00097820 RIV/00216305:26620/17:PU125465 RIV/62156489:43210/17:43912029

Výsledek na webu

<a href="http://journals.sagepub.com/doi/pdf/10.1177/1010428317711656" target="_blank" >http://journals.sagepub.com/doi/pdf/10.1177/1010428317711656</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/1010428317711656" target="_blank" >10.1177/1010428317711656</a>

Jazyk výsledku

angličtina

Název v původním jazyce

VPA does not enhance platinum binding to DNA in cisplatin-resistant neuroblastoma cancer cells

Popis výsledku v původním jazyce

Neuroblastoma represents a malignancy of the sympathetic nervous system characteristic by biological heterogeneity. Thus, chemotherapy exhibits only low effectivity in curing high-risk forms. Previous studies revealed the cytotoxic potential of valproate on neuroblastoma cells. Nevertheless, these studies omitted effects of hypoxia, despite its undeniable tumorigenic role. In this study, we addressed the question whether valproate promotes binding of platinumbased anti-cancer drugs (cisplatin, carboplatin and oxaliplatin) to DNA and role of hypoxia, cellular antioxidant capacity and cisplatin resistance in this process. Following parameters differed significantly when cells were exposed to treatment with platinum-based drugs: elevation of platinum content bound to DNA, elevation of total thiol content, GSH/GSSG ratio, glutathione reductase and peroxidase, superoxide dismutase and elevation of antioxidant capacity. Hypoxia caused a decrease in cytosine/adenine peak, and no changes in platinum-DNA binding properties were observed. After valproate co-treatment, oxidative stress-related parameters and cytosine/adenine peak were only elevated. The amount of platinum bound to DNA was not changed significantly. Valproate is not able to enhance platinum binding to DNA in neuroblastoma cells, neither in case of intrinsic resistance (UKF-NB-4) nor in case of acquired resistance (UKF-NB4CDDP). Therefore, another mechanism different from increase in platinum binding to DNA should be considered as a synergistic effect of valproate by cisplatin treatment.

Název v anglickém jazyce

VPA does not enhance platinum binding to DNA in cisplatin-resistant neuroblastoma cancer cells

Popis výsledku anglicky

Neuroblastoma represents a malignancy of the sympathetic nervous system characteristic by biological heterogeneity. Thus, chemotherapy exhibits only low effectivity in curing high-risk forms. Previous studies revealed the cytotoxic potential of valproate on neuroblastoma cells. Nevertheless, these studies omitted effects of hypoxia, despite its undeniable tumorigenic role. In this study, we addressed the question whether valproate promotes binding of platinumbased anti-cancer drugs (cisplatin, carboplatin and oxaliplatin) to DNA and role of hypoxia, cellular antioxidant capacity and cisplatin resistance in this process. Following parameters differed significantly when cells were exposed to treatment with platinum-based drugs: elevation of platinum content bound to DNA, elevation of total thiol content, GSH/GSSG ratio, glutathione reductase and peroxidase, superoxide dismutase and elevation of antioxidant capacity. Hypoxia caused a decrease in cytosine/adenine peak, and no changes in platinum-DNA binding properties were observed. After valproate co-treatment, oxidative stress-related parameters and cytosine/adenine peak were only elevated. The amount of platinum bound to DNA was not changed significantly. Valproate is not able to enhance platinum binding to DNA in neuroblastoma cells, neither in case of intrinsic resistance (UKF-NB-4) nor in case of acquired resistance (UKF-NB4CDDP). Therefore, another mechanism different from increase in platinum binding to DNA should be considered as a synergistic effect of valproate by cisplatin treatment.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NV15-28334A" target="_blank" >NV15-28334A: Vliv metalothioneinů na vazbu platinových cytostatik na DNA v nádorových buňkách</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Tumor Biology

ISSN

1010-4283

e-ISSN

—

Svazek periodika

39

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

1-8

Kód UT WoS článku

—

EID výsledku v databázi Scopus

2-s2.0-85031416298