Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells.
10.1007/s11655-015-2280-5
- Author:
Xin FANG
1
;
Xiao-Liang MIAO
2
;
Jun-Li LIU
2
;
Dong-Wei ZHANG
3
;
Min WANG
4
;
Dan-Dan ZHAO
3
;
Qian-Qian MU
1
;
Na YU
1
;
Fang-Fang MO
3
;
Hong-Ping YIN
4
;
Si-Hua GAO
5
Author Information
1. School of Basic Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
2. Fraser Laboratories for Diabetes Research, Department of Medicine, RI-McGill University Health Centre, Montreal, Quebec, H4A3J1, Canada.
3. Diabetes Research Center, Beijing University of Chinese Medicine, Beijing, 100029, China.
4. School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.
5. School of Basic Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China. gaosihua1216@163.com.
- Publication Type:Journal Article
- Keywords:
Chinese medicine;
apoptosis;
apoptosis inducing factor pathway;
berberine;
cytochrome C/Apaf-1/caspase-3;
mouse insulinoma cells
- From:
Chinese journal of integrative medicine
2019;25(11):853-860
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate apoptotic effects of berberine, a significant alkaloids component existing in Rhizoma coptidis, and its possible acting mechanism in insulinoma cells.
METHODS:Different concentrations of berberine were used to treat mouse insulinoma (MIN6) cells for various period of time. The viability and apoptosis of the cells were analyzed using methylthiazolyldiphenvl-tetrazolium bromide assay, flow cytometry and enzyme-linked immuno sorbent assay. Changes in the relating pro- and anti-apoptosis proteins were detected by western-blotting.
RESULTS:The half-maximal inhibitory concentration (IC) of berberine was 5.7 μmol/L on MIN6 cells viability for 16 h. Berberine caused a 20% reduction (P<0.05) in cell number after only 4-h incubation; which reached 50% after 24 h (P<0.01). Berberine treatment for 16 h significantly increased the level of DNA fragmentation. The flow cytometry showed the apoptotic rate increased 2.9- and 4.6-fold after treating with berberine (5 μmol/L) for 8 and 16 h, while 3- and 8.7-fold after 10 μmol/L treatment for 8 and 16 h (P<0.01). Berberine treatment dramatically elevated the expression ratio of Bax to Bcl-2. Meanwhile, berberine notably increased the apoptosis-inducing factors and cytochrome C transforming from the mitochondria to the cytoplasm. Apoptotic protease-activating factor 1 (Apaf-1) was subsequently activated after cytochrome C release. Furthermore, caspase-3 and poly adenosine diphosphate-ribose polymerase were also activated to trigger apoptosis cascade.
CONCLUSION:High concentration (5 and 10 μmol/L) of berberine could induce the apoptosis of MIN6 cells through cytochrome C/Apaf-1/caspase-3 and apoptosis inducing factor (AIF) pathway.
