Hyperthermia potentiates cisplatin cytotoxicity and negative effects on mitochondrial functions in OVCAR-3 cells
Autor: | Saulius Paškauskas, Sonata Trumbeckaite, Vida Mildaziene, Laima Degutyte-Fomins, Arturas Sukovas, Rasa Baniene, Giedre Silkuniene, Aldona Jasukaitiene, Antanas Gulbinas, Zilvinas Dambrauskas |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Hyperthermia Physiology Oxidative phosphorylation Adenocarcinoma Mitochondrion Pharmacology Oxidative Phosphorylation Cell Line 03 medical and health sciences Oxygen Consumption 0302 clinical medicine Glutamate Dehydrogenase medicine Humans Cytotoxicity Ovarian Neoplasms Cisplatin Chemistry Glutamate dehydrogenase Glutamate receptor Hyperthermia Induced Cell Biology medicine.disease Mitochondria Neoplasm Proteins 030104 developmental biology Cell culture 030220 oncology & carcinogenesis Mitochondrial Membranes Female medicine.drug |
Zdroj: | Journal of Bioenergetics and Biomembranes. 51:301-310 |
ISSN: | 1573-6881 0145-479X |
DOI: | 10.1007/s10863-019-09805-8 |
Popis: | The aim of this study was to determine the effects of hyperthermia, cisplatin and their combination on mitochondrial functions such as glutamate dehydrogenase (GDH) activity and mitochondrial respiration rates, as well as survival of cultured ovarian adenocarcinoma OVCAR-3 cells. Cells treated for 1 h with hyperthermia (40 and 43 °C) or cisplatin (IC50) or a combination of both treatments were left for recovery at 37 °C temperature for 24 h or 48 h. The obtained results revealed that 43 °C hyperthermia potentiated effects of cisplatin treatment: combinatory treatment more strongly suppressed GDH activity and expression, mitochondrial functions, and decreased survival of OVCAR-3 cells in comparison to separate single treatments. We obtained evidence that in the OVCAR-3 cell line GDH was directly activated by hyperthermia (cisplatin eliminated this effect); however, this effect was followed by GDH inhibition after 48 h recovery. A combination of 43 °C hyperthermia with cisplatin induced stronger GDH inhibition in comparison to separate treatments, and negative effects exerted on GDH activity correlated with suppression of mitochondrial respiration with glutamate + malate. Cisplatin did not induce uncoupling of oxidative phosphorylation in OVCAR-3 cells but induced impairment of the outer mitochondrial membrane in combination with 43 °C hyperthermia. Hyperthermia (43 °C) potentiated cytotoxicity of cisplatin in an OVCAR-3 cell line. |
Databáze: | OpenAIRE |
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