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World J Gastroenterol. 2006 Jan 7;12(1):21-8.

Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line.

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  • 1School of Chinese Medicine, China Medical University, Taichung City 404, Taiwan. China.

Abstract

AIM:

To investigate the relationship between the inhibited growth (cytotoxic activity) of berberine and apoptotic pathway with its molecular mechanism of action.

METHODS:

The in vitro cytotoxic techniques were complemented by cell cycle analysis and determination of sub-G1 for apoptosis in human gastric carcinoma SNU-5 cells. Percentage of viable cells, cell cycle, and sub-G1 group (apoptosis) were examined and determined by the flow cytometric methods. The associated proteins for cell cycle arrest and apoptosis were examined by Western blotting.

RESULTS:

For SNU-5 cell line, the IC50 was found to be 48 micromol/L of berberine. In SNU-5 cells treated with 25-200 micromol/L berberine, G2/M cell cycle arrest was observed which was associated with a marked increment of the expression of p53, Wee1 and CDk1 proteins and decreased cyclin B. A concentration-dependent decrease of cells in G0/G1 phase and an increase in G2/M phase were detected. In addition, apoptosis detected as sub-G0 cell population in cell cycle measurement was proved in 25-200 micromol/L berberine-treated cells by monitoring the apoptotic pathway. Apoptosis was identified by sub-G0 cell population, and upregulation of Bax, downregulation of Bcl-2, release of Ca2+, decreased the mitochondrial membrane potential and then led to the release of mitochondrial cytochrome C into the cytoplasm and caused the activation of caspase-3, and finally led to the occurrence of apoptosis.

CONCLUSION:

Berberine induces p53 expression and leads to the decrease of the mitochondrial membrane potential, Cytochrome C release and activation of caspase-3 for the induction of apoptosis.

PMID:
16440412
PMCID:
PMC4077487
[PubMed - indexed for MEDLINE]
Free PMC Article
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