Abstract | UNLABELLED: It is known that glycolysis contributes to the survival of tumor cells by providing them with energetic and plastic substrates. Dichloroacetate (DCA) as inhibitor of kinase pyruvate dehydrogenase shifts balance of energy metabolism of tumor cells from aerobic glycolysis towards oxidative phosphorylation. The aim of the study was to investigate cytostatic/cytotoxic effect of DCA on glioma C6 cells at the conditions of different oxygenation of the cell incubation medium. MATERIALS AND METHODS: RESULTS: By the data of in vitro cytotoxicity, upon hypoxia IC50 value of DCA was three times lower (p < 0.05) than that upon normoxic conditions (18.2 ± 3.9 mM vs. 51.2 ± 8.1 mM). Hypoxia itself enhanced the ROS production in glioma cells by 113.5% (p < 0.05) that correlated with increase of apoptosis by 292% (p < 0.05). In hypoxic glioma C6 cells DCA did not significantly influence the ROS production, but decreased hypoxia-induced apoptosis by 3.5-6.5 times (p < 0.05) and significantly increased cell death rates via necrosis (p < 0.05). In contrast to hypoxia, upon the conditions of hyperoxia IC50 values for DCA did not differ from the corre-sponding values upon the normoxia conditions and at 30% and 95% oxygen content were equal to 35.8 ± 7.2 mM and 42.3 ± 5.1 mM respectively. CONCLUSION:
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Authors | D L Kolesnik, O N Pyaskovskaya, I V Boichuk, G I Solyanik |
Journal | Experimental oncology
(Exp Oncol)
Vol. 36
Issue 4
Pg. 231-5
(Dec 2014)
ISSN: 1812-9269 [Print] Ukraine |
PMID | 25537215
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Reactive Oxygen Species
- Lactic Acid
- Dichloroacetic Acid
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
- Cell Hypoxia
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Dichloroacetic Acid
(pharmacology)
- Glioma
- Humans
- Hyperoxia
- Hypoxia
(metabolism)
- Inhibitory Concentration 50
- Lactic Acid
(biosynthesis)
- Necrosis
- Neoplasms
(drug therapy, metabolism)
- Reactive Oxygen Species
(metabolism)
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