Ganoderic acid A holds promising cytotoxicity on human glioblastoma mediated by incurring apoptosis and autophagy and inactivating PI3K/AKT signaling pathway

Ganoderic acid A (GA-A), recognized as a lanostanetriterpene isolated from Ganoderma lucidum, demonstrates an efficient antitumor activity in multiple cancers. To date, it is unclear whether and how GA-A functions on human glioblastoma (GBM). To unravel the functional significance of GA-A on human glioblastoma (GBM), the cell-counting kit-8 and transwell assays were used to detect proliferation, migration, and invasion of human GBM cell after GA-A treatment. Then, we utilized the flow cytometry and western blot to further evaluate the effect of GA-A on GBM cell. Further, activities of Autophagy and PI3K/Akt signaling were assessed by Western blot assay. We found that GA-A significantly inhibited proliferation, migration, and invasion of GBM cell. Additionally, GA-A markedly triggered cell Apoptosis, which incarnated an elevation trend in apoptotic percentage, simultaneously, an increased level of proapoptosis protein (Bax and active Caspase-3) and a decreased level of antiapoptosis protein (Bcl-2), induced by GA-A treatment. Meanwhile, levels of two well-known Autophagy markers (beclin 1 and LC3 II) increased while another autophagic substrate (P-62) was reduced. Moreover, the expressions levels of phosphorylated Akt, mTOR, p-P70S6K, and cyclin D1 in the PI3K/Akt pathway were significantly reduced, which revealed GA-A repressed the activation of PI3K/Akt signaling pathway. Collectively, these results indicate that GA-A may encourage U251 cell growth and invasion/migration inhibition, Apoptosis, and Autophagy through the inactivation of PI3K/Akt signaling pathway in human GBM. Hence, GA-A may be a potent antitumorigenic agent for human GBM in future clinical practice.