Ustusolate E and 11α-Hydroxy-Ustusolate E induce apoptosis in cancer cell lines by regulating the PI3K/AKT/mTOR and p-53 pathways.
10.1016/S1875-5364(25)60840-5
- Author:
Mewlude REHMUTULLA
1
;
Sitian ZHANG
1
;
Jie YIN
1
;
Jianzheng HUANG
1
;
Yang XIAO
1
;
Zhengxi HU
2
,
3
;
Qingyi TONG
4
;
Yonghui ZHANG
5
Author Information
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.
2. 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. Electronic address: hzx616@
3. com.
4. 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. Electronic address: qytong@hust.edu.cn.
5. 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. Electronic address: zhangyh@mails.tjmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
11α-Hydroxy-ustusolate E;
Cancer;
PI3K/AKT/mTOR pathway;
Ustusolate E;
p-53 Pathway
- MeSH:
Humans;
Apoptosis/drug effects*;
TOR Serine-Threonine Kinases/genetics*;
Proto-Oncogene Proteins c-akt/genetics*;
Cell Line, Tumor;
Phosphatidylinositol 3-Kinases/genetics*;
Signal Transduction/drug effects*;
Tumor Suppressor Protein p53/genetics*;
Cell Proliferation/drug effects*;
Antineoplastic Agents/pharmacology*;
Sesquiterpenes/pharmacology*;
Aspergillus/chemistry*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(3):346-353
- CountryChina
- Language:English
-
Abstract:
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 Aspergilluscalidoustus 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 G2/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.
