Glycyrrhetinic acid combined with doxorubicin induces apoptosis of human hepatocellular carcinoma HepG2 cells by regulating ERMMDs.
10.19540/j.cnki.cjcmm.20250311.702
- Author:
Ming-Shi PANG
1
;
Xiu-Yun BAI
1
;
Jue YANG
1
;
Rong-Jun DENG
1
;
Xue-Qin YANG
2
;
Yuan-Yan LIU
1
Author Information
1. School of Chinese Materia Medica, Beijing University of Chinese Medicine Beijing 102400, China.
2. Institute of Health Preservation in Traditional Chinese Medicine, School of Traditional Chinese Medicine, Beijing University of Chinese Medicine Beijing 102400, China Key Laboratory of Traditional Chinese Medicine Health Sciences,Ministry of Education Beijing 102400, China Beijing Key Laboratory of Traditional Chinese Medicine Health Sciences Beijing 102400, China.
- Publication Type:Journal Article
- Keywords:
Ca~(2+) transfer;
apoptosis;
doxorubicin;
endoplasmic reticulum-mitochondrial membrane domains;
glycyrrhetinic acid
- MeSH:
Humans;
Apoptosis/drug effects*;
Hep G2 Cells;
Glycyrrhetinic Acid/pharmacology*;
Doxorubicin/pharmacology*;
Liver Neoplasms/genetics*;
Carcinoma, Hepatocellular/physiopathology*;
Mitochondria/metabolism*;
Endoplasmic Reticulum/metabolism*;
Cell Survival/drug effects*;
Membrane Proteins/genetics*
- From:
China Journal of Chinese Materia Medica
2025;50(11):3088-3096
- CountryChina
- Language:Chinese
-
Abstract:
This study investigates the effect of glycyrrhetinic acid(GA) combined with doxorubicin(DOX) on apoptosis in HepG2 cells and its possible mechanisms. HepG2 cells were cultured in vitro, and cell viability was assessed using the cell counting kit-8(CCK-8) method. Flow cytometry was used to measure apoptosis levels in HepG2 cells. The cells were divided into the following groups: control group(0 μmol·L~(-1)), DOX group(2 μmol·L~(-1)), GA group(150 μmol·L~(-1)), and DOX + GA combination group(2 μmol·L~(-1) DOX + 150 μmol·L~(-1) GA), with treatments given for 24 hours. The colocalization level between the endoplasmic reticulum(ER) and mitochondria was assessed by colocalization fluorescence imaging. Fluorescence probes were used to measure the Ca~(2+) content in the ER and mitochondria. The qRT-PCR and Western blot were used to determine the mRNA and protein expression of sirtuin-3(SIRT3). Co-immunoprecipitation(CO-IP) was applied to investigate the interactions between voltage-dependent anion channel 1(VDAC1) and SIRT3, as well as between VDAC1, glucose-regulated protein 75(GRP75), and inositol 1,4,5-trisphosphate receptor(IP3R). The results showed that the combination of DOX and GA promoted apoptosis in HepG2 liver cancer cells. The colocalization level between the ER and mitochondria was significantly reduced, the Ca~(2+) content in the ER was significantly increased, and the Ca~(2+) content in the mitochondria was significantly decreased. The relative expression of VDAC1, GRP75, and IP3R was significantly reduced, and interactions between VDAC1, GRP75, and IP3R were observed. SIRT3 mRNA and protein expression levels were significantly increased, and an interaction between SIRT3 and VDAC1 was detected. The acetylation level of VDAC1 was significantly decreased. In conclusion, GA combined with DOX induces apoptosis in HepG2 cells by mediating the deacetylation of VDAC1 through SIRT3, weakening the interactions among VDAC1, GRP75, and IP3R. This regulates the formation of endoplasmic reticulum-mitochondrial membrane domains(ERMMDs), affects Ca~(2+) transport between the ER and mitochondria, and ultimately triggers cell apoptosis.
