α-Hederin Induces Apoptosis in Hepato-cellular Carcinoma Cells by Activating and Stabilizing p53/Noxa Signaling Pathway
10.3870/j.issn.1004-0781.2024.03.002
- VernacularTitle:α-常春藤皂苷通过激活和稳定p53/Noxa信号诱导肝癌细胞凋亡
- Author:
Xiaojing CHEN
1
;
Li ZHOU
;
Kaiqi LIU
;
Jufeng DUAN
;
Ming LIU
;
Hongliang LI
;
Xuanbin WANG
Author Information
1. 湖北医药学院附属人民医院药学部和药学院,十堰 442000
- Keywords:
α-hederin;
Hepatocellular carcinoma;
Apoptosis;
p53;
Noxa
- From:
Herald of Medicine
2024;43(3):334-345
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effects and mechanisms of α-hederin,an active ingredient in Fruc-tus Akebiae,on hepatocellular carcinoma(HCC)cells.Methods HCC cells were divided into four groups and treated with α-hederin(0,10,20,and 30 μmol·L-1)for 24 h and 48 h,respectively.MTT assays were used to detect the cell proliferation rate,flow cytometry(FCM)was used to detect the apoptotic rate,transcriptomics was used to screen signaling pathways in α-hederin-treated HCC cells,RNA interference was exploited to verify the underlying signaling pathway,and real-time quantitative PCR(qRT-PCR)and Western blotting(WB)were used to detect expression changes of the mRNA and protein of TP53(p53),PMAIP1(Noxa),and apoptosis-associated proteins,Caspase9 and Caspase3.Results α-Hederin induced apoptosis by activa-ting apoptosis-associated proteins,PARP,Caspase9 and Caspase3.Transcriptomics,qRT-PCR,and WB results also showed that α-hederin increased the mRNA and protein expression of p53 and Noxa.Furthermore,α-hederin inhibited the protein degradation of p53 and Noxa,reversing the apoptosis decrease in p53/Noxa siRNA-knocked-down HCC cells.In vivo results showed that α-hederin inhibited the growth of HCC tumors.Conclusion α-hederin may induce the apoptosis of HCC cells by activating and stabilizing the p53/Noxa signaling pathway.