Tricyclic Antidepressants Modulate Stressed Mitochondria in Glioblastoma Multiforme Cells.

Abstract

A common feature of solid tumors, including glioblastoma multiforme (GBM), is mitochondrial dysfunction. However, it is reported that the current standard of anti-GBM therapies may potentiate mitochondrial damage and, in effect, support the aggressive character of cancer. As mitochondria are implicated in the modulation of cellular drug sensitivity and chemoresistance mechanisms, activation-stressed mitochondria in GBM cells may represent a new target for anti-GBM therapy that is nontoxic for normal cells.Methods:As mitochondria are possible targets for antidepressant drugs used as adjuvant therapy in patients with GBM, we examined their influence on mitochondrial volume and activity, reactive oxygen species level, extracellular lactate concentration, and p65 NF-κB gene expression in GBM cells.Results:Our investigation showed, for the first time, that tricyclic antidepressants, imipramine and amitriptyline, partially reverse GBM abnormalities.Conclusion:In the light of reported studies, the mitochondrial disturbance observed in glioma cells is a dynamic process that can be reversed or silenced. Moreover, imipramine and amitriptyline are attractive cellular metabolic modulators and can potentially be used to restoring a proper function of mitochondria in GBM cells.