Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway

• 作者: Xiangjin Zheng Wan Li Huanli Xu Jinyi Liu Liwen Ren Yihui Yang Sha Li Jinhua Wang Tengfei Ji Guanhua Du
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（11）
• 所属期刊栏目: Origimal articles
• 页码范围: 3465-3480
• 页数: 16页
• 语种: 英文

摘要

Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sinomenium acutum,showed that it had inhibitory effects on several kinds of cancer.Here,we synthesized a sinomenine derivative,sino-wcj-33(SW33),tested it for antitumor activ-ity on GBM and explored the underlying mechanism.SW33 significantly inhibited proliferation and col-ony formation of GBM and reduced migration and invasion of U87 and U251 cells.It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis.Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse ef-fects on the body.SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR path-ways.Thus,SW33 appears to be a promising drug for treating GBM effectively and safely.