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@article{1391657, author = {Raudenská, Martina and Krejcova, Ludmila and Richtera, Lukas and Heger, Zbynek and Hrabeta, Jan and Eckschlager, Tomas and Stiborova, Marie and Adam, Vojtech and Kratochvílová, Monika and Masařík, Michal and Gumulec, Jaromír}, article_location = {London}, article_number = {9}, doi = {http://dx.doi.org/10.1177/1010428317711656}, keywords = {Neuroblastoma; cisplatin; resistance; valproate; hypoxia; oxidative stress}, language = {eng}, issn = {1010-4283}, journal = {Tumor Biology}, title = {VPA does not enhance platinum binding to DNA in cisplatin-resistant neuroblastoma cancer cells}, volume = {39}, year = {2017} }
TY - JOUR ID - 1391657 AU - Raudenská, Martina - Krejcova, Ludmila - Richtera, Lukas - Heger, Zbynek - Hrabeta, Jan - Eckschlager, Tomas - Stiborova, Marie - Adam, Vojtech - Kratochvílová, Monika - Masařík, Michal - Gumulec, Jaromír PY - 2017 TI - VPA does not enhance platinum binding to DNA in cisplatin-resistant neuroblastoma cancer cells JF - Tumor Biology VL - 39 IS - 9 SP - 1-8 EP - 1-8 PB - Sage Publications INC SN - 10104283 KW - Neuroblastoma KW - cisplatin KW - resistance KW - valproate KW - hypoxia KW - oxidative stress N2 - 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 platinum-based 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-NB-4CDDf'). Therefore, another mechanism different from increase in platinum binding to DNA should be considered as a synergistic effect of valproate by cisplatin treatment. ER -
RAUDENSKÁ, Martina, Ludmila KREJCOVA, Lukas RICHTERA, Zbynek HEGER, Jan HRABETA, Tomas ECKSCHLAGER, Marie STIBOROVA, Vojtech ADAM, Monika KRATOCHVÍLOVÁ, Michal MASAŘÍK a Jaromír GUMULEC. VPA does not enhance platinum binding to DNA in cisplatin-resistant neuroblastoma cancer cells. \textit{Tumor Biology}. London: Sage Publications INC, 2017, roč.~39, č.~9, s.~1-8. ISSN~1010-4283. Dostupné z: https://dx.doi.org/10.1177/1010428317711656.
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