Yao Yueliang, Sun Si, Cao Mianfu, Mao Min, He Jiang, Gai Qujing, Qin Yan, Yao Xiaoxue, Lu Huimin, Chen Fanglin, Wang Wenying, Luo Min, Zhang Hua, Huang Hongbo, Ju Jianhua, Bian Xiu-Wu, Wang Yan
Department of Pathology, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
ACS Chem Neurosci. 2020 Aug 5;11(15):2256-2265. doi: 10.1021/acschemneuro.0c00206. Epub 2020 Jul 8.
Glioblastoma multiforme (GBM) is the most malignant form of glioma, and the overall survival time of patients with GBM is usually less than 14 months. Therefore, it is urgent to find new and effective medicine for GBM. Recently, marine natural products have been shown to exhibit strong inhibitory effects on cancer cells, providing a new avenue for exploring novel drugs for GBM treatment. In this study, we investigated the inhibitory effect of the Grincamycin (GCN) B-F, newly isolated from marine-derived Streptomyces Lusitanus SCSIO LR32, on GBM cells, and evaluated the mechanism of GCN B on GBM. The results, for the first time, showed that GCN B acted as a potent inhibitor to suppress growth and invasion of two human GBM cell lines U251 and 091214 . In addition, GCN B could effectively target GSCs in GBM evidenced by attenuated formation of tumor spheres and decrease of several markers of GSCs. Furthermore, we performed gene expression microarray followed by Signal-Net analysis. The result revealed that RHOA and PI3K/AKT axis played critical roles for a GCN B-mediated inhibitory effect on GSCs. Altogether, our findings highlighted GCN B as a promising inhibitor for GSCs via targeting RHOA and PI3K/AKT.
