Magnolol induces cytotoxic autophagy in glioma by inhibiting PI3K/AKT/mTOR signaling

Glioma is difficult-to-treat because of its infiltrative nature and the presence of the blood-brain barrier. Temo-zolomide is the only FDA-approved drug for its management. Therefore, finding a novel chemotherapeutic agent for glioma is of utmost importance. Magnolol, a neolignan, has been known for its apoptotic role in glioma. In this work, we have explored a novel anti-glioma mechanism of Magnolol associated with its role in autophagy modulation. We found increased expression levels of Beclin-1, Atg5-Atg12, and LC3-II and lower p62 expression in Magnolol-treated glioma cells. PI3K/AKT/mTOR pathway proteins were also downregulated in Magnolol-treated glioma cells. Next, we treated the glioma cells with Insulin, a stimulator of PI3K/AKT/mTOR signaling, to confirm that Magnolol induced autophagy by inhibiting this pathway. Insulin reversed the effect on Magnolol-mediated autophagy induction. We also established the same in in vivo glioma model where Magnolol showed an anti-glioma effect by inducing autophagy. To confirm the cytotoxic effect of Magnolol-induced autophagy, we used Chloroquine, a late-stage autophagy inhibitor. Chloroquine efficiently reversed the anti-glioma effects of Magnolol both in vitro and in vivo. Our study revealed the cytotoxic effect of Magnolol-induced autophagy in glioma, which was not previously reported. Additionally, Magnolol showed no toxicity in non-cancerous cell lines as well as rat organs. Thus, we concluded that Magnolol is an excellent candidate for developing new therapeutic strategies for glioma management.

Automated summary

Glioma is difficult to treat due to its invasive nature and the blood-brain barrier. This study discovered that Magnolol, a neolignan, plays an important role in inducing apoptosis and modulating autophagy in glioma cells. The study also found that Magnolol inhibits the PI3K/AKT/mTOR pathway to induce autophagy. The results suggest that Magnolol could be a promising therapeutic agent for glioma management.