Inhibition of TRPM7 by glutathione decreases oxidant and apoptotic action of cisplatin through the downregulation of Ca2+ and Zn2+ in glioblastoma cells.

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Cisplatin (CiSP)-mediated stimulation of TRPM7 may induce oxidant and apoptotic activities through the upregulation of Ca2+, apoptosis, and reactive oxygen species (ROS) in glioblastoma (DBTRG-05MG) cells, whereas inhibition of TRPM7 by the antioxidant glutathione (GSH) may reduce the observed increases in DBTRG-05MG. The aim of the study was to examine how TRPM7 activation stimulates DBTRG-05MG cell death but also how it inhibits the effects of TRPM7 antagonists (GSH and carvacrol, CRV) via altering ROS toxicity and apoptosis. In the DBTRG-05MG, 5 groups were established: control, GSH (10 mM for 2h), CiSP (25 μM for 24h), CiSP+GSH, and CiSP+CRV (200 mM for 24h). The amounts of cytosolic free Ca2+ were further increased in the CiSP group by the stimulation of TRPM7 (naltriben), even though the GSH and CRV treatments caused them to decrease in the cells. The amounts of mitochondrial membrane hyperpolarization, ROS, death cell, apoptosis, free zinc ion, and caspase-3, -8, and -9 in the cells were higher in the CiSP than in the control and GSH, although their amounts were lower in the CiSP+GSH and CiSP+CRV than in the CiSP only. The CiSP-induced decreases in cell viability and GSH concentrations were increased by GSH incubation. The stimulation of TRPM7 increased the anticancer action of CiSP, although its inhibition decreased the amount of CiSP-induced oxidative stress and DBTRG-05MG deaths through the treatment of GSH and CRV. TRPM7 stimulation could be considered a potential tumor killer channel through oxidative glioblastoma damage caused by CiSP.