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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Berberine induces apoptosis in p53-null leukemia cells by down-regulating XIAP at the post-transcriptional level
Jian Liu1, Xiaoling Zhang, Aiguo Liu
1Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan P.R. China.
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.
Insights
Berberine triggers apoptosis in leukemia cells lacking p53 by downregulating XIAP. This mechanism enhances sensitivity to chemotherapy, offering a novel therapeutic strategy for leukemia.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Berberine exhibits anticancer properties via various mechanisms.
- The precise molecular pathways of berberine-induced apoptosis independent of p53 are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of berberine-induced apoptosis in p53-null leukemia cells.
- To investigate the role of XIAP and MDM2 in this process.
Main Methods:
- Utilized p53-null leukemia cell line (EU-4 cells) treated with berberine.
- Assessed cell viability and apoptosis.
- Employed Western blot, PCR, and small interfering RNA (siRNA) to analyze XIAP and MDM2 expression and function.
Main Results:
- Berberine induced p53-independent apoptosis mediated by XIAP in leukemia cells.
- Berberine suppressed XIAP protein levels in a dose- and time-dependent manner, involving MDM2 inhibition and proteasomal degradation.
- Inhibition of XIAP increased leukemia cell sensitivity to doxorubicin.
Conclusions:
- Characterized berberine's mechanism for caspase activation and apoptosis induction in p53-deficient leukemia.
- Berberine shows potential as a novel apoptosis-inducing agent for leukemia lacking p53 expression.
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