Figure 5.

The scheme of TMZ and MGMT effects. In non-cancerous, as well as in glioma cells, TMZ introduces alkylating changes at the DNA, such as O⁶meG methylation. In the case of an unmethylated MGMT promoter, the MGMT enzyme is expressed and transfers the methyl-group to itself, repairing the DNA (left). Cells with the methylated MGMT promoter do not or only marginally express MGMT. In this case, the DNA damage persists and may trigger apoptosis or cytotoxicity (right). The schematic diagram was partially created with biorender.com (a). A summary of the experimental results. ↑ = upregulation, ↓ = downregulation (b). Abbreviations: HGA, astrocytoma, isocitrate dehydrogenase mutant, CNS WHO grade 4; MGMT, O⁶-methylguanine-DNA-methyltransferase; MGMT+, the glioblastoma cell line with >50% MGMT promoter methylation; MGMT-, the glioblastoma cell line without MGMT promoter methylation; O⁶meG, O⁶-methylated Guanine; TMZ, temozolomide; and w, weeks.