Ustusolate E and 11α-Hydroxy-Ustusolate E induce apoptosis in cancer cell lines by regulating the PI3K/AKT/mTOR and p-53 pathways  

作　　者：Mewlude Rehmutulla Sitian Zhang Jie Yin Jianzheng Huang Yang Xiao Zhengxi Hu Qingyi Tong Yonghui Zhang 

机构地区：[1]Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation,School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Chinese Journal of Natural Medicines》2025年第3期346-353,共8页中国天然药物(英文版)

基　　金：supported by the Program for Changjiang Scholars of the Ministry of Education of the People's Republic of China(No.T2016088);the National Natural Science Foundation for Distinguished Young Scholars(No.81725021);the National Key R&D Program of China(No.2021YFA0910500);the Science and Technology Major Project of Hubei Province(No.2021ACA012);the Innovative Research Groups of the National Natural Science Foundation of China(No.81721005);the Academic Frontier Youth Team of HUST(No.2017QYTD19);the Fundamental Research Funds for the Central Universities(No.2172019kfyXJS166).

摘　　要：Cancer represents a significant disease that profoundly impacts human health and longevity.Projections indicate a 47%increase in the global cancer burden by 2040 compared to 2020,accompanied by a further rise in the associated economic burden.Consequently,there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer.Natural products(NPs)play a crucial role in the identification and development of anticancer therapeutics.This study identified ustusolate E(UE)and its analog 11α-hydroxy-ustusolate E(HUE)from strain Aspergillus calidoustus TJ403-EL05,and examined their antitumor activities and mechanisms of action.The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS(human gastric cancer cells)and 786-O(human renal clear cell carcinoma cells),induced irreversible DNA damage,blocked the cell cycle at the G_(2)/M phase,and further induced apoptosis in tumor cells.To the best of the authors’knowledge,this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms.The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.

关 键 词：Ustusolate E 11α-Hydroxy-ustusolate E Cancer PI3K/AKT/mTOR pathway p-53 Pathway 

分 类 号：R73[医药卫生—肿瘤]