A novel Diels–Alder adduct of mulberry leaves exerts anticancer effect through autophagy-mediated cell death  

作　　者：Yu-han Shu Hua-hua Yuan Meng-ting Xu Ye-ting Hong Cheng-cheng Gao Zhi-pan Wu Hao-te Han Xin Sun Rui-lan Gao Si-fu Yang Shou-xin Li Jing-kui Tian Jian-bin Zhang 

机构地区：[1]College of Biomedical Engineering and Instrument Science,Zhejiang University,Hangzhou,310058,China [2]Clinical Research Institute,Zhejiang Provincial People’s Hospital,People’s Hospital of Hangzhou Medical College,Hangzhou,310014,China [3]Hangzhou Medical College,Hangzhou,310053,China [4]Department of Oncology,Zhejiang Provincial People’s Hospital,People’s Hospital of Hangzhou Medical College,Hangzhou,310014,China [5]Department of Hematology,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,310006,China [6]Key Laboratory for Biomedical Engineering of Ministry of Education,Zhejiang-Malaysia Joint Research Center for Traditional Medicine,Zhejiang University,Hangzhou,310058,China

出　　处：《Acta Pharmacologica Sinica》2021年第5期780-790,共11页中国药理学报（英文版）

基　　金：This work was supported by the National Science and Technology Major Project of China (2019ZX09301004);Zhejiang Provincial Science and Technology Planning Project (2016C04005) to JKT;Zhejiang Provincial Outstanding Talent Project of Ten Thousand Talents Program,Zhejiang Provincial Qianjiang Talents Program,Zhejiang Provincial Natural Science Foundation (LR18H160002);Traditional Chinese Medicine Scientific Research Fund Project of Zhejiang Province(2018ZB010);Zhejiang Provincial Program in Medicine and Health Sciences and Technology (2018253645) to JBZ;National Natural Science Foundation of China (81703907) to XS;Zhejiang Provincial Program in Medicine and Health Sciences and Technology (2018KY223) to SFY.

摘　　要：Guangsangon E (GSE) is a novel Diels–Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP–LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as “autophagy-mediated cell death.” Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.

关 键 词：Guangsangon E AUTOPHAGY ER stress respiratory cancer 

分 类 号：R285[医药卫生—中药学]