Stimulation of TRPM2 Channel in Glioblastoma Tumour Cells by Gallic Acid Potentiated the Anti-Tumour and Oxidant Effects of Doxorubicin

Abstract

Current treatments for glioblastoma (GBM), defined as the brain and spinal cord tumour with the worst prognosis in adults, do not sufficiently improve the prognosis. Therefore, there is a clear need to investigate the possible molecular pathways of tumour proliferation and metastasis and new strategic approaches for its treatment. In this study, we aimed to elucidate the synergistic chemotherapeutic activity of gallic acid (GA) with doxorubicin (DOX) in human glioblastoma tumour cells (DBTRG) and the molecular mechanisms of these effects. For this purpose, we investigated the stimulatory role of GA on DOX-induced human glioblastoma tumour cell (DBTRG) death via TRPM2 channel activation. For the study, five groups were formed from DBTRG cells as Control, GA (4O mu M), DOX (1 mu M), GA + DOX, and ACA + DOX (ACA, 25 mu M). In the analyses made, Total Antioxidant/Oxidant/ (TAS and TOS) status, cell viability, lipid peroxidation levels, glutathione peroxidase (GSH-Px) and glutathione (GSH) enzyme activity, caspase activity, reactive oxygen species (ROS), inflammation markers, Poly ADP Ribose Polymerase-1, (PARP-1), and Transient Receptor Potential Melastatin 2 (TRPM2) levels in the cells were determined. DOX treatment reduced TAS, GSH, GSH-Px, and cell viability levels while increasing inflammatory indicators, TOS, ROS, MDA, caspase, PARP-1, and TRPM2 levels and causing DBTRG cell cytotoxicity. The treatment was even more successful when GA and DOX were used together. In conclusion, the increase in cell death and ROS levels mediated by TRPM2 activation in DOX DBTRG cells was further enhanced by GA treatment.