Celastrus orbiculatus Extract Promotes Apoptosis of Gastric Cancer Cells by Destroying Mitochondrial Structure
10.13422/j.cnki.syfjx.20221823
- VernacularTitle:南蛇藤提取物通过破坏线粒体结构促进胃癌AGS细胞凋亡的机制
- Author:
Haibo WANG
1
;
Yuanyuan LUO
1
;
Xinyi FENG
1
;
Tengyang NI
1
;
Zewen CHU
1
;
Miao ZHU
1
;
Yanqing LIU
1
Author Information
1. Medical College， The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine，Yangzhou University-Yangzhou Cancer Research Institute， Yangzhou University， Yangzhou 225001， China
- Publication Type:Journal Article
- Keywords:
Celastrus orbiculatus extract;
mitochondria;
gastric cancer;
apoptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(18):46-53
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the inhibitory effect of Celastrus orbiculatus extract （COE） on gastric cancer cells， to clarify the specific mechanism of COE promoting the apoptosis of gastric cancer cells by affecting the mitochondrial structure and function， and to provide an experimental basis for the further development and clinical application of C. orbiculatus. MethodBrdu staining combined with flow cytometry and Annexin V-fluorescein isothiocyanate （AnnexinV-FITC） staining combined with flow cytometry were employed to detect the effects of COE （20， 40， 80 mg·L-1） on the proliferation and apoptosis of gastric cancer cells， respectively. The changes in mitochondrial membrane potential were detected with JC-1 mitochondrial membrane potential assay kit. The expression of apoptosis-associated proteins including B-cell lymphoma-2 （Bcl-2）， B-cell lymphoma-xL （Bcl-xL）， Bcl-2-associated X （Bax）， and cysteine aspartutespecific protease-3 （Caspase-3） in gastric cancer cells was determined by Western blot. Transmission electron microscopy was employed to detect changes in the mitochondrial microstructure of gastric cancer cells exposed to COE. Western blot was employed to measure the expression of mitochondrial marker proteins ［superoxide dismutase 1 （SOD1）， voltage-dependent anion channel （VDAC）， prohibitin 1 （PHB1）， and heat shock protein 60 （HSP60）］ in gastric cancer cells. ResultCompared with the control group， COE （40， 80 mg·L-1） inhibited the proliferation and promoted the apoptosis of gastric cancer cells （P<0.05）. Furthermore， COE reduced the mitochondrial membrane potential of gastric cancer cells. Compared with the control group， COE （20， 40， 80 mg·L-1） up-regulated the expression of Bax and Caspase-3 which promoted apoptosis of gastric cells （P<0.05， P<0.01）， and COE at 40 and 80 mg·L-1 down-regulated the expression of Bcl-2 and Bcl-xL which inhibited the apoptosis of gastric cancer cells （P<0.01）. The results of transmission electron microscopy showed that COE changed the microstructure of gastric cancer cells， which led to the appearance of vacuoles in the cell membrane and mitochondria and damaged the mitochondrial structure. Compared with the control group， COE （20， 40， 80 mg·L-1） changed the expression of mitochondrial marker proteins. Specifically， it up-regulated the expression of SOD1 involved in stress response （P<0.05， P<0.01） and down-regulated that of VDAC， PHB1， and HSP60 associated with mitochondrial stability and permeability （P<0.01）. ConclusionCOE can significantly inhibit the proliferation and promote the apoptosis of gastric cancer cells. It may activate the mitochondrial apoptosis pathway by destroying the mitochondrial structure and function of gastric cancer cells.
