Arsenic trioxide-induced apoptosis of human malignant lymphoma cell lines and its mechanisms.
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.


CONCLUSIONS
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.
Lu
Di
D
Department of Cell Biology, First Military Medical University, Guangzhou 510515, China. ludi2004@hotmail.com
Bai
Xiao-chun
XC
Gui
Li
L
Li
Ming
M
Zheng
Wei-shen
WS
Han
Xi-qun
XQ
Luo
Shen-qiu
SQ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D010087:Oxides / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051020:bcl-X Protein
D000970:Antineoplastic Agents; D001152:Arsenicals; C494811:BCL2L1 protein, human; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077237:Arsenic Trioxide