Cepharanthine inhibits the proliferation of glioblastoma cells by blocking the autophagy-lysosomal pathway

Cepharanthine (CEP) is a Stephania cepharantha-derived bioactive alkaloid that can inhibit the progression of numerous tumors. However, the effects and specific mechanisms of CEP performance in glioblastoma (GBM) remain unclear. Thus, this study focused on exploring the effects of CEP on GBM and clarifying the underlying mechanisms. U251 and U87 cells were selected to estimate the anti-GBM effects of CEP, and the possible targets of CEP were analyzed using RNA Sequencing (RNA-seq). Validation experiments based on RNA-seq data were performed to clarify the key pathway by which CEP mediates GBM cells response. Results showed that CEP administration successfully inhibited the proliferation and induced the cell cycle arrest and Apoptosis of the GBM cells. RNA-seq analysis after CEP administration identified 386 differentially expressed genes, which were highly enriched in the autophagy-lysosomal pathway. Subsequent findings demonstrated that CEP exhibited the potential to curb GBM progression by causing lysosomal and autophagic dysfunction. Taken together, our results indicate that CEP is a potential drug candidate for GBM intervention.

Autophagy; Cepharanthine; Glioblastoma; Lysosome.