Grincamycin B Functions as a Potent Inhibitor for Glioblastoma Stem Cell via Targeting RHOA and PI3K/AKT

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 vitro. 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.