1. Cyclooxygenase (COX) Inhibition by Acetyl Salicylic Acid (ASA) Enhances Antitumor Effects of Nitric Oxide in Glioblastoma In Vitro
- Author
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Jessica Guenzle, Nicklas W C Garrelfs, Astrid Weyerbrock, and Jonathan M Goeldner
- Subjects
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 - Abstract
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.
- Published
- 2019
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