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Cell Physiol Biochem. 2013;32(5):1213-24. doi: 10.1159/000354520. Epub 2013 Nov 14.

Berberine induces apoptosis in p53-null leukemia cells by down-regulating XIAP at the post-transcriptional level.

Author information

1
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan P.R. China.

Abstract

BACKGROUND:

Berberine exerts anticancer activities both in vitro and in vivo through different mechanisms. However, the underlying molecular mechanisms of berberine induced p53-independent apoptosis remain unclear.

METHODS:

The p53-null leukemia cell line EU-4 cells were exposed to berberine. Then the cell viability and apoptosis were determined. Western blot and PCR were employed to detect the expression of apoptosis related protein, XIAP and MDM2. Small interfering RNA (siRNA) was applied to knock down endogenous expression of MDM2 and XIAP.

RESULTS:

Berberine induced p53-independent, XIAP-mediated apoptotic cell death in p53-null leukemia cells. Treatment with berberine resulted in suppression of XIAP protein in a dose- and time- dependent manner. Berberine induced down-regulation of XIAP protein involving inhibition of MDM2 expression and a proteasome-dependent pathway. Moreover, inhibition of XIAP by berberine or siRNA increased the sensitivity of leukemia cells to doxorubicin-induced apoptosis.

CONCLUSION:

Our findings characterize the molecular mechanisms of berberine-induced caspase activation and subsequent apoptosis, and berberine may be a novel candidate inducer of apoptosis in leukemia cells, which normally lack p53 expression.

PMID:
24335171
DOI:
10.1159/000354520
[Indexed for MEDLINE]
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