Effect of hypoxic and hyperbaric oxygen conditions on cytotoxic action of modified isothiourea derivative (ZKK-3) against T98G glioblastoma cell line

• Autorzy: Stepien K. , Ostrowski T.P. , Pucko E.B. , Kazimierczuk Z. , Matyja E.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Gliomas, derived from astroglial cells, constitute about 50% of all brain tumours. The hypoxic state of neoplastic tissue is regarded to be an important reason of treatment failure with chemo- and radiotherapy. The aim of this study was to examine if administration of gas mixture with increased and decreased oxygen content will result in changes of cytotoxic properties of modified isothiourea derivative (ZKK-3) against human glioblastoma tumour in vitro. METHODS: The experiment was performed on human glioblastoma T98G cell line, which were cultured in hypoxic (for 24 hours) or hyperbaric oxygen conditions (HBO, 1 hour of hyperbaric oxygen under the pressure of 3 ATA, then 23 hours of normoxia) in a medium containing selected modified isothiourea derivative: N,N’- dimethyl-S-(2,3,4,5,6-pentabromobenzyl)-isothiouronium bromide (ZKK-3). Control cultures were preserved in standard conditions. The viability of the cells was evaluated after 24 and 48 hours using CellTiter 96® AQueous One Solution Cell Proliferation Assay (Promega). Cell proliferation was assessed after 24 hours by Multisizer 3 Beckman Coulter. RESULTS: Glioma cells subjected to hypoxia conditions were significantly more resistant to cytotoxic action of ZKK-3. The proliferative rate of neoplastic glioma cells appeared not to be affected when the cultures were exposed to low oxygen partial pressure. The HBO treatment resulted in enhancement of anti-tumour properties of tested isothiourea derivative, evidenced by a decrease in T98G cells viability and growth. CONCLUSIONS: Hypoxia culture conditions reduce the therapeutic effect of ZKK-3 and promote glioma cells survivability, which is possibly associated with the induction of drug resistance. Increase of sensitivity of glioma cells to the tested agent after administration of hyperbaric oxygen allows to consider HBO as a promising therapeutic strategy for patients with gliomas. The research was supported by the KNOW-MMRC project.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S67-S68

Twórcy

autor

Stepien K.

• Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Ostrowski T.P.

• Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Pucko E.B.

• Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Kazimierczuk Z.

• Department of Chemistry, Warsaw University of Life Sciences, Warsaw, Poland

autor

Matyja E.

• Department of Experimental and Clinical Neuropathology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland