Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, and currently chemotherapeutic options for GBM are very limited. Given the poor prognosis, the development of novel anti-GBM agents is quite urgent. Using two human glioma cells (U87 and A172 cells), we demonstrated that Icariside II (ICA II), an active flavonoid compound derived from Epimedium koreanum, could inhibit GBM cell growth in a dose dependent manner. Wound healing data suggested that ICA II also inhibited the migration of human glioma cells. Mechanistically, ICA II induced apoptosis and cell cycle arrest, and this cytotoxic effect was dependent on the reduction of Forkhead box O3a(FOXO3a) phosphorylation mediated by Akt and the enrichment of nuclear FOXO3a, which initiated the transcription of p21/p27. Importantly, the cytotoxic effect induced by ICA II could be reversed by silencing the expression of FOXO3a, suggesting the critical role of FOXO3a in this process. Taken together, we propose ICA II as a potential novel anti-GBM candidate with a mechanism of inhibiting cell proliferation and inducing apoptosis through suppressing Akt activation and potentiating FOXO3a activity.
Keywords: FOXO3a; Glioma; Icariside II; apoptosis; p21.