In this study, we explore whether CAP, a cocktail of reactive oxygen and nitrogen species, can amplify the cytotoxic effect on both TMZ-sensitive and TMZ-resistant glioblastoma multiforme (GBM) in three-dimensional tumor-like tissues through inhibiting the glutathione (GSH)/ glutathione peroxidase 4 (GPX4) antioxidant machinery, which can further lead to DNA damage. This evidence concerns the gene GPX4 and glioblastoma.