Xanthatin suppresses proliferation and tumorigenicity of glioma cells through autophagy inhibition via activation of the PI3K ‐Akt–mTOR pathway

In this study, we report that xanthatin suppressed glioma cells proliferation and induced apoptosis in a time- and concentration-dependent manner, and was accompanied by autophagy inhibition displaying a significantly reduced LC3 punctate fluorescence and LC3II/I ratio, decreased level of Beclin 1, while increased accumulation of p62. Notably, treating glioma cells with xanthatin resulted in obvious activation of the PI3K-Akt –mTOR signaling pathway, as indicated by increased mTOR and Akt phosphorylation, decreased ULK1 phosphorylation, which is important in modulating autophagy. Furthermore, xanthatin-mediated pro-apoptosis in glioma cells was significantly reversed by autophagy inducers (rapamycin or Torin1), or PI3K -mTOR inhibitor NVP-BEZ235. Taken together, these findings indicate that anti-proliferation and pro-apoptosis effects of xanthatin in glioma are most likely by inhibiting autophagy via activation of PI3K-Akt–mTOR pathway, suggesting a potential therapeutic strategy against glioma.

Source: Pharmacology Research and Perspectives - December 27, 2022 Category: Drugs & Pharmacology Authors: Huaqing Chen, Tong Zhu, Xiaojie Huang, Wenshuang Xu, Zemin Di, Yuyang Ma, Min Xue, Sixing Bi, Yujun Shen, Yongqiang Yu, Yuxian Shen, Lijie Feng Tags: INVITED REVIEW Source Type: research