Department of Pediatrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing Research Center for Prevention & Control of Maternal and Child Diseases and Public Health, Chongqing 401147, China.
National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Toxicol Appl Pharmacol. 2024 Dec;493:117141. doi: 10.1016/j.taap.2024.117141. Epub 2024 Nov 3.
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.
石蒜裂碱（CEP）是一种来源于石蒜属植物的生物活性生物碱，能够抑制多种肿瘤的进展。然而，CEP 对神经胶质瘤（GBM）的作用及其具体机制尚不清楚。因此，本研究旨在探讨 CEP 对 GBM 的影响，并阐明其潜在机制。本研究选用 U251 和 U87 细胞来评估 CEP 对 GBM 的抑制作用，并通过 RNA 测序（RNA-seq）分析 CEP 的可能作用靶点。同时，基于 RNA-seq 数据进行验证实验，以阐明 CEP 介导 GBM 细胞反应的关键途径。结果表明，CEP 处理可成功抑制 GBM 细胞的增殖，并诱导细胞周期停滞和凋亡。CEP 处理后的 RNA-seq 分析鉴定出 386 个差异表达基因，这些基因高度富集于自噬-溶酶体途径。进一步的研究表明，CEP 通过引起溶酶体和自噬功能障碍，具有抑制 GBM 进展的潜力。综上所述，本研究结果表明，CEP 是一种有潜力的 GBM 干预药物候选物。
