Nitidine chloride inhibits the malignant behavior of human glioblastoma cells by targeting the PI3K/AKT/mTOR signaling pathway.

Abstract

Recent studies have demonstrated that nitidine chloride (NC), a natural bioactive alkaloid, displays potent antitumor activity in various types of cancer. In the present study, NC was examined for efficacy in the treatment of human glioblastoma multiforme (GBM) as well as the molecular basis for its more general inhibitory effects in cancer. U251 and U87 GBM cell lines were exposed to three concentrations of NC (5, 25 and 50µM) invitro, and tumor cell growth was assessed on the basis of proliferation, migration and energy metabolism. Decreases in viability and proliferation reached ~50% for both cell lines with 50µM NC at 24h as assessed by cell viability Cell Counting Kit-8 (CCK-8) and EdU assays. In wound closure and Transwell assays, migration and invasion were inhibited at 50µM after 24h (~20 and 80%, respectively; P<0.05). ATP and L-lactate levels were also decreased after treatment with NC (50µM, 24h; P<0.05 and P<0.01, respectively). Finally, in western blot analysis, phosphorylation of Akt and mTOR was suppressed by NC, but partially restored when cells were treated simultaneously with a novel Akt activator, SC79. Partial restoration was also observed in viability/proliferation (U251 and U87, ~15 vs. 40%; NC vs. NC+SC79; P<0.05) and invasion (U251 and U87, ~30 vs. 60%; NC vs. NC+SC79; P<0.05). Our results demonstrated that NC inhibits development of GBM by targeting the PI3K/Akt/mTOR signaling pathway and provides a potential therapeutic agent for the treatment of GBM.