Glioblastoma tumorspheres treated with streptonigrin (Sn) and temozolomide (TMZ)

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor, with a median survival of less than two years despite standard therapy. Transglutaminase 2 (TGM2) contributes to tumor progression and poor clinical outcomes. This study evaluated the therapeutic potential of combining streptonigrin (SN), a TGM2 inhibitor, with temozolomide (TMZ), the standard chemotherapeutic agent for GBM. The combination of SN and TMZ significantly reduced cell viability and ATP levels and induced apoptosis more effectively than either agent alone. Moreover, the combination effectively reduced stemness and invasiveness in GBM TSs, along with the expression of related proteins and mRNAs. In vivo, combination therapy prolonged survival in mice and reduced expression of invasiveness-related protein, as shown by immunohistochemistry. These findings suggest that targeting TGM2 with SN enhances the therapeutic efficacy of TMZ in GBM. The combination of SN and TMZ holds promise as a novel treatment strategy for GBM.