Chinese agarwood petroleum ether extract suppressed gastric cancer progression via up-regulation of DNA damage-induced G0/G1 phase arrest and HO-1-mediated ferroptosis.
10.1016/S1875-5364(25)60876-4
- Author:
Lishan OUYANG
1
;
Xuejiao WEI
1
;
Fei WANG
1
;
Huiming HUANG
1
;
Xinyu QIU
1
;
Zhuguo WANG
1
;
Peng TAN
1
;
Yufeng GAO
1
;
Ruoxin ZHANG
1
;
Jun LI
2
;
Zhongdong HU
3
Author Information
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China; Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
2. School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
3. Modern Research Center for Traditional Chinese Medicine, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: zdhu@bucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Chinese agarwood petroleum ether extract (CAPEE);
DNA damage-p21-Cyclin D1/CDK4 signaling axis;
Ferroptosis;
G(0)/G(1) phase arrest;
Gastric cancer;
HO-1
- MeSH:
Animals;
Humans;
Mice;
Antineoplastic Agents, Phytogenic;
Apoptosis/drug effects*;
Cell Line, Tumor;
Cyclin D1/genetics*;
Cyclin-Dependent Kinase 4/genetics*;
DNA Damage/drug effects*;
Drugs, Chinese Herbal/pharmacology*;
Ferroptosis/drug effects*;
G1 Phase Cell Cycle Checkpoints/drug effects*;
Heme Oxygenase-1/genetics*;
Mice, Inbred BALB C;
Mice, Nude;
Plant Extracts/pharmacology*;
Stomach Neoplasms/physiopathology*;
Thymelaeaceae/chemistry*;
Up-Regulation/drug effects*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(10):1210-1220
- CountryChina
- Language:English
-
Abstract:
Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC50) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G0/G1 phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe2+, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
