Synergistic increase in anti-cancer stemness activity and pro-apoptotic effects in human glioblastoma cancer stem-like cells by combination treatment with temozolomide and corosolic acid

Glioblastoma (GB) is a highly aggressive brain cancer with poor prognosis and a five-year survival rate of only 4-5%, largely due to challenges in surgical removal and radiotherapy limitations. Corosolic acid (CA), a natural pentacyclic triterpene, exhibits promising anti-cancer activity against GB. In this study, we founded that GBM8401-derived cancer stem cells (GBM8401-CSCs) display increased stemness, proliferation, migration, invasion, and elevated cancer stemness factors (Nestin, OCT4, CD133) compared to parental cells. CA treatment dose-dependently inhibited these malignant features and downregulated key cancer stemness genes. Combined with Temozolomide (TMZ), CA synergistically suppressed GBM8401-CSCs growth, colony formation, migration, invasion, and promoted apoptosis more effectively than either CA or TMZ alone and significantly reduced sphere formation and cancer stemness gene expression. Molecular docking results show a strong affinity of TMZ and CA for CD133 and OCT4 proteins, highlighting distinct molecular interactions. These results suggest that CA, especially in combination with TMZ, holds therapeutic potential for targeting human GB-CSCs.