Columbianadin suppresses glioblastoma progression by inhibiting the PI3K-Akt signaling pathway

• Published in: Biochemical pharmacology 2024-05, Vol.223, p.116112, Article 116112
• Main Authors: Zhang, Wei, Dong, Jianhong, Xu, Jiayun, Qian, Yiming, Chen, Danni, Fan, Ziwei, Yang, Hao, Xiang, Jianglei, Xue, Xiumin, Luo, Xuan, Jiang, Yuanyuan, Wang, Yongjie, Huang, Zhihui
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Columbianadin; Coumarins; Glioblastoma; Glioblastoma - metabolism; Mice; Network pharmacology; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt; Proliferation; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction
• ISSN: 0006-2952; 1873-2968; 1873-2968
• DOI: 10.1016/j.bcp.2024.116112

[Display omitted] Glioblastoma (GBM) is the most common malignant glioma among brain tumors with low survival rate and high recurrence rate. Columbianadin (CBN) has pharmacological properties such as anti-inflammatory, analgesic, thrombogenesis-inhibiting and anti-tumor effects. However, it remains unknown that the effect of CBN on GBM cells and its underlying molecular mechanisms. In the present study, we found that CBN inhibited the growth and proliferation of GBM cells in a dose-dependent manner. Subsequently, we found that CBN arrested the cell cycle in G0/G1 phase and induced the apoptosis of GBM cells. In addition, CBN also inhibited the migration and invasion of GBM cells. Mechanistically, we chose network pharmacology approach by screening intersecting genes through targets of CBN in anti-GBM, performing PPI network construction followed by GO analysis and KEGG analysis to screen potential candidate signaling pathway, and found that phosphatidylinositol 3-kinase/Protein Kinase-B (PI3K/Akt) signaling pathway was a potential target signaling pathway of CBN in anti-GBM. As expected, CBN treatment indeed inhibited the PI3K/Akt signaling pathway in GBM cells. Furthermore, YS-49, an agonist of PI3K/Akt signaling, partially restored the anti-GBM effect of CBN. Finally, we found that CBN inhibited GBM growth in an orthotopic mouse model of GBM through inhibiting PI3K/Akt signaling pathway. Together, these results suggest that CBN has an anti-GBM effect by suppressing PI3K/Akt signaling pathway, and is a promising drug for treating GBM effectively.