About: Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells     Goto   Sponge   Distinct   Permalink

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  • Etoposide (Vepesid, VP-16), an inhibitor of topoisomerase II, is a chemotherapeutic drug commonly used for treatment of different types of malignant diseases. By inhibiting the topoisomerase II enzyme activity in cancer cells, this drug leads to DNA damage and subsequently to cell death. In this study, we investigated the effect of this anticancer drug alone and in combination with a histone deacetylase (HDAC) inhibitor, valproic acid (VPA), on a human UKF-NB-4 neuroblastoma cell line. The results of the study demonstrate that UKF-NB-4 neuroblastoma cells are sensitive both to etoposide and to VPA. They also indicate that the impact of VPA on cytotoxicity of etoposide in these tumor cells varies depending on the sequence of cultivation of the cells with the drugs. As a suitable sequence of cultivation, with a high rate of suppression of neuroblastoma cell growth was found the preincubation of the cells with etoposide, which was followed by their cultivation with VPA. In contrast, the reversed combination (preincubation of the cells with VPA before their treating with etoposide) did not give any increase in etoposide cytotoxicity. The effect of such combined treatment can be explained by measuring the cell cycle distribution, which shows that both etoposide and VPA change the cell cycle phase distribution. Etoposide and VPA were found as cycle phase specific drugs that are cytotoxic to human UKF-NB-4 neuroblastoma cells used either as single drugs or both together. However, whereas VPA might sensitize the cells to etoposide, inappropriate sequence of cultivation of the cells with VPA can decrease the etoposide cytotoxic efficacy. The results found here warrant further studies of combined treatment of neuroblastoma cells with etoposide with HDAC inhibitors and may help in the design of new protocols geared to the treatment of high risk neuroblastomas.
  • Etoposide (Vepesid, VP-16), an inhibitor of topoisomerase II, is a chemotherapeutic drug commonly used for treatment of different types of malignant diseases. By inhibiting the topoisomerase II enzyme activity in cancer cells, this drug leads to DNA damage and subsequently to cell death. In this study, we investigated the effect of this anticancer drug alone and in combination with a histone deacetylase (HDAC) inhibitor, valproic acid (VPA), on a human UKF-NB-4 neuroblastoma cell line. The results of the study demonstrate that UKF-NB-4 neuroblastoma cells are sensitive both to etoposide and to VPA. They also indicate that the impact of VPA on cytotoxicity of etoposide in these tumor cells varies depending on the sequence of cultivation of the cells with the drugs. As a suitable sequence of cultivation, with a high rate of suppression of neuroblastoma cell growth was found the preincubation of the cells with etoposide, which was followed by their cultivation with VPA. In contrast, the reversed combination (preincubation of the cells with VPA before their treating with etoposide) did not give any increase in etoposide cytotoxicity. The effect of such combined treatment can be explained by measuring the cell cycle distribution, which shows that both etoposide and VPA change the cell cycle phase distribution. Etoposide and VPA were found as cycle phase specific drugs that are cytotoxic to human UKF-NB-4 neuroblastoma cells used either as single drugs or both together. However, whereas VPA might sensitize the cells to etoposide, inappropriate sequence of cultivation of the cells with VPA can decrease the etoposide cytotoxic efficacy. The results found here warrant further studies of combined treatment of neuroblastoma cells with etoposide with HDAC inhibitors and may help in the design of new protocols geared to the treatment of high risk neuroblastomas. (en)
Title
  • Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells
  • Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells (en)
skos:prefLabel
  • Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells
  • Impact of histone deacetylase inhibitor valproic acid on the anticancer effect of etoposide on neuroblastoma cells (en)
skos:notation
  • RIV/00216208:11310/12:10128676!RIV13-GA0-11310___
http://linked.open...avai/predkladatel
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  • I, P(GAP301/10/0356), S
http://linked.open...iv/cisloPeriodika
  • Suppl 3
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
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  • 140629
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  • RIV/00216208:11310/12:10128676
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  • cell cycle; cytotoxicity; neuroblastoma; valproic acid; etoposide (en)
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  • SE - Švédské království
http://linked.open...ontrolniKodProRIV
  • [F32BFF431CA8]
http://linked.open...i/riv/nazevZdroje
  • Neuroendocrinology Letters
http://linked.open...in/vavai/riv/obor
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http://linked.open...vavai/riv/projekt
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 33
http://linked.open...iv/tvurceVysledku
  • Eckschlager, Tomáš
  • Hraběta, Jan
  • Poljaková, Jitka
  • Stiborová, Marie
  • Groh, Tomáš
issn
  • 0172-780X
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  • 11310
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