Cyclooxygenase (COX) Inhibition by Acetyl Salicylic Acid (ASA) Enhances Antitumor Effects of Nitric Oxide in Glioblastoma In Vitro
| Autor: | Jessica Guenzle, Nicklas W C Garrelfs, Astrid Weyerbrock, Jonathan M Goeldner |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Time Factors Cell Survival Angiogenesis Neuroscience (miscellaneous) Brain tumor Antineoplastic Agents Nitric Oxide Piperazines Nitric oxide Necrosis 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Glioma medicine Humans Cyclooxygenase Inhibitors Nitric Oxide Donors Aspirin biology Drug Synergism Glutathione medicine.disease Up-Regulation 030104 developmental biology Neurology chemistry Apoptosis biology.protein Cancer research Cyclooxygenase Glioblastoma Azo Compounds 030217 neurology & neurosurgery Salicylic acid |
| Zdroj: | Molecular Neurobiology. 56:6046-6055 |
| ISSN: | 1559-1182 0893-7648 |
| Popis: | Glioblastoma multiforme (GBM) is the most aggressive brain tumor with a high recurrence rate and a median survival of about 16 months even with multimodal therapy. Novel experimental strategies against malignant gliomas include cyclooxygenase (COX) inhibition and nitric oxide (NO)-based therapies. Therapeutic doses of NO can be delivered to tumor cells by NO donors such as JS-K (O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate) which releases NO upon enzymatic activation by glutathione S-transferase. COX-2 is frequently overexpressed in tumors and increases tumor invasiveness and angiogenesis. In this study, we show that pretreatment with acetyl salicylic acid (ASA) enhanced the cytotoxic antitumor effect of NO in vitro. Combination of low doses of JS-K and ASA revealed a dose-dependent synergistic increase of necrotic cell death under circumvention of classical apoptosis and alteration of the metabolic calcium level. These findings provide an opportunity to improve currently used therapeutic strategies in the treatment of gliomas with a well-established remedy. |
| Databáze: | OpenAIRE |
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