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Arsenic trioxide-induced apoptosis of human malignant lymphoma cell lines and its mechanisms
1Department of Cell Biology, First Military Medical University, Guangzhou 510515, China. ludi2004@hotmail.com
Objective:
To investigate the responses of human Burkitt lymphoma cells to arsenic trioxide (As2O3) and the possible mechanisms.
Methods:
Epstein-Barr virus (EBV)-positive human B-lymphoma Raji cell line and EBV-negative human B-lymphoma BJAB cell line were used as in vitro models to assess the cell apoptosis by morphology and DNA agarose gel electrophoresis. Protein expression was analyzed using Western blotting.
Results:
After 24-hour treatment with the 2, 5 and 10 micromol/L As2O3, the concentrations of As2O3 achievable in vivo, cell apoptosis was induced in human Burkitt lymphoma BJAB cells at the rates of 47.6%+/-4.8% (Mean+/-SD, n=3), 66.4%+/-5.1%, 87.0%+/-7.3% and at 35.5%+/-3.8%, 51.5%+/-6.2%, 62.2%+/-7.9% respectively in Raji cells, corresponding to the concentration of As2O3. EBV-infected Raji cell line was less sensitive to As2O3 than EBV-negative BJAB cell line (P<0.05). As2O3-induced apoptosis was accompanied by down-regulation of Bcl-xL protein expression and activation of apoptosis protein caspase-3, as identified by Western blotting.
Conclusion:
As2O3 exerts apoptosis-inducing effects on human Burkitt lymphoma cells through down-regulation of Bcl-xL protein expression and activation of apoptosis protein caspase-3, and may serve as a candidate therapeutic agent against malignant lymphoma for both systemic and local therapies.
