Berberine Induces Cell Apoptosis through Cytochrome C/Apoptotic Protease-Activating Factor 1/Caspase-3 and Apoptosis Inducing Factor Pathway in Mouse Insulinoma Cells.

Autor: Fang X; School of Basic Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.; Fraser Laboratories for Diabetes Research, Department of Medicine, RI-McGill University Health Centre, Montreal, Quebec, H4A3J1, Canada., Miao XL; Fraser Laboratories for Diabetes Research, Department of Medicine, RI-McGill University Health Centre, Montreal, Quebec, H4A3J1, Canada.; School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China., Liu JL; Fraser Laboratories for Diabetes Research, Department of Medicine, RI-McGill University Health Centre, Montreal, Quebec, H4A3J1, Canada., Zhang DW; Diabetes Research Center, Beijing University of Chinese Medicine, Beijing, 100029, China., Wang M; School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China., Zhao DD; Diabetes Research Center, Beijing University of Chinese Medicine, Beijing, 100029, China., Mu QQ; School of Basic Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China., Yu N; School of Basic Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China., Mo FF; Diabetes Research Center, Beijing University of Chinese Medicine, Beijing, 100029, China., Yin HP; School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China., Gao SH; School of Basic Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China. gaosihua1216@163.com.; Diabetes Research Center, Beijing University of Chinese Medicine, Beijing, 100029, China. gaosihua1216@163.com.
Jazyk: angličtina
Zdroj: Chinese journal of integrative medicine [Chin J Integr Med] 2019 Nov; Vol. 25 (11), pp. 853-860. Date of Electronic Publication: 2015 Jul 04.
DOI: 10.1007/s11655-015-2280-5
Abstrakt: 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 50 ) 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.
Databáze: MEDLINE
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