Spironolactone Induces Apoptotic Cell Death in Human Glioblastoma U87-MG Cancer Cells

Abstract

Background: Spironolactone is a conventional drug widely in use for the treatment of heart failure and hypertension patients. On the other side recent studies have reported spironolactone can prevent growth and drug resistance in cancer stem cells (CSCs), by inhibiting DNA double-strand break (DSB) repair; suggesting its potential application in cancer therapy. Objectives: Our study aimed at assessing the potential cytotoxicity of spironolactone in human U87-MG glioblastoma cells. Methods: different concentrations of spironolactone (0 - 50 μM) for 48 and 72 h were used for treatment. Cell viability assay was carried out by the 4, 5-dimethylthiazole-2-yl, 2, 5-diphenyl tetrazolium (MTT) method. Apoptosis was evaluated using annexin V/PI staining and flow cytometry and colorimetric measurement of caspase 8 and 9 activity. Results: our findings showed a significant dose-dependent cytotoxic effect of spironolactone with maximum effect in 30 μM (P-value < 0.05). Spironolactone can induce approximately 20% apoptotic cell death in U87-MG cancer cells which were mainly related to early apoptotic cells. Indeed, the activity of caspase 8 and 9 was significantly elevated in spironolactone-treated cells compared to mock control. Conclusions: Findings showed the cytotoxic effect of spironolactone in U87-MG glioblastoma cancer cells in a mechanism dependent on apoptosis cell death induction. Our findings suggest the potential application of spironolactone in the treatment of glioblastoma in vitro.