Angi-16. Meclofenamate-Induced Dysregulation of Calcium Homeostasis and Cytoskeletal Dynamics Contributes to Malignant Glioma Invasiveness

PURPOSE Malignant gliomas exhibit highly invasive behavior, partly driven by dysregulated intracellular Ca2+ signaling and cytoskeletal remodeling. Meclofenamate (MFA), a non-steroidal anti-inflammatory drug (NSAID) known to inhibit gap junctions and ion channels, has emerged as a candidate modulator of tumor cell physiology. In this study, we aimed to investigate the impact of MFA on Ca2+ homeostasis, cytoskeletal integrity, and glioma cell invasiveness. RESULTS The ratiometric Ca2+ imaging results show that MFA exhibited a biphasic effect on intracellular Ca2+ levels during application: an initial increase within the first 5 minutes followed by a progressive decline. Interestingly, this Ca2+-elevating effect persisted even in the absence of extracellular Ca2+, suggesting involvement of intracellular Ca2+ stores. Repeated MFA exposure produced only Ca2+ suppression, indicating a desensitization or depletion mechanism in glioma cells. The Ca2+-modulating effects of MFA were dose-dependent (30-100 μM). Prolonged (120 min) MFA exposure led to a striking redistribution of βIII-tubulin (TUBB3), shifting from a diffuse cytoplasmic pattern to a perinuclear localization, consistent with cytoskeletal disorganization. Furthermore, MFA significantly reduced glioma cell viability and inhibited migration after 24-72 hour applications, highlighting its potential as an anti-invasive agent. CONCLUSION MFA perturbs intracellular Ca2+ signaling in a biphasic and dose-dependent manner and induces cytoskeletal reorganization in glioma cells. These effects are associated with reduced cell viability and migratory capacity. Our findings suggest that MFA may impair glioma invasiveness by disrupting Ca2+-dependent cytoskeletal dynamics, warranting further investigation as a therapeutic modulator in glioma treatment.