Pristimerin induces Noxa-dependent apoptosis by activating the FoxO3a pathway in esophageal squamous cell carcinoma.
10.1016/S1875-5364(25)60865-X
- Author:
Mengyuan FENG
1
;
Anjie ZHANG
2
;
Jingyi WU
2
;
Xinran CHENG
3
;
Qingyu YANG
3
;
Yunlai GONG
3
;
Xiaohui HU
3
;
Wentao JI
3
;
Xianjun YU
4
;
Qun ZHAO
5
Author Information
1. School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China; Department of Gastroenterology, Taihe Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan 442000, China; Inflammation-Cancer Transformation and Wudang Chinese Medicine Research, Hubei Talent Introduction and Innovation Demonstration Base, School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China.
2. School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China; Inflammation-Cancer Transformation and Wudang Chinese Medicine Research, Hubei Talent Introduction and Innovation Demonstration Base, School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China.
3. School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China.
4. School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China; Department of Gastroenterology, Taihe Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan 442000, China; Inflammation-Cancer Transformation and Wudang Chinese Medicine Research, Hubei Talent Introduction and Innovation Demonstration Base, School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China. Electronic address: xjyu@hbmu.edu.cn.
5. School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China; Inflammation-Cancer Transformation and Wudang Chinese Medicine Research, Hubei Talent Introduction and Innovation Demonstration Base, School of Pharmacy, Hubei University of Medicine, Shiyan 442000, China. Electronic address: zhaoqun@hbmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
ESCC;
FoxO3a;
Noxa;
Pristimerin
- MeSH:
Forkhead Box Protein O3/genetics*;
Humans;
Apoptosis/drug effects*;
Esophageal Squamous Cell Carcinoma/physiopathology*;
Esophageal Neoplasms/physiopathology*;
Pentacyclic Triterpenes;
Animals;
Cell Line, Tumor;
Proto-Oncogene Proteins c-bcl-2/genetics*;
Mice;
Signal Transduction/drug effects*;
Mice, Nude;
Cell Proliferation/drug effects*;
Triterpenes/pharmacology*;
Xenograft Model Antitumor Assays;
Mice, Inbred BALB C;
Male;
Gene Expression Regulation, Neoplastic/drug effects*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(5):585-592
- CountryChina
- Language:English
-
Abstract:
Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
