Hydrogen peroxide in the Burkitt's lymphoma cell line Raji provides protection against arsenic trioxide-induced apoptosis via the phosphoinositide-3 kinase signalling pathway.
Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined the effects of hydrogen peroxide (H(2)O(2)) on arsenic trioxide (As(2)O(3))-induced cell killing. Low concentrations of H(2)O(2) (200 micromol/l) inhibited the ability of As(2)O(3) to induce apoptosis in the Burkitt's lymphoma cell line Raji. H(2)O(2) altered the form of cell death from apoptosis to pyknosis/necrosis and also lowered the degree of cell killing by As(2)O(3). H(2)O(2) was capable of preventing caspase-3 activation induced by As(2)O(3) in Raji cells. Incubation of cells with a phosphoinositide-3 kinase (PI-3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H(2)O(2) on As(2)O(3)-induced caspase-3 activation. In addition, the PI-3K inhibitor partially blocked the effects of H(2)O(2) on up-regulation of Bcl-2 and Bcl-X(L) protein expression, down-regulation of Bax protein expression, and phosphorylation of Bcl-2 and IkappaBalpha. This investigation demonstrated for the first time that low concentrations of H(2)O(2) provide protection against the in vivo of As(2)O(3)-induced apoptosis. PI-3K plays a crucial role in enhancing cell survival during H(2)O(2), inhibiting As(2)O(3)-induced apoptosis in the Burkitt's lymphoma cells. As(2)O(3)-induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol.
Lu
Di
D
Department of Cell Biology, The First Military Medical University, Guangzhou, China.
Bai
Xiao-Chun
XC
Gui
Li
L
Su
Yong-Chun
YC
Deng
Fan
F
Liu
Bin
B
Li
Xiu-Mei
XM
Zeng
Wei-Sen
WS
Cheng
Bao-Luan
BL
Luo
Shen-Qiu
SQ
D000730:Androstadienes / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000201:enzymology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D010087:Oxides / Q000627:therapeutic use*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D000077191:Wortmannin; D051020:bcl-X Protein
D000730:Androstadienes; D000970:Antineoplastic Agents; D000077237:Arsenic Trioxide; D001152:Arsenicals; D053148:Caspase 3; D020169:Caspases; D006861:Hydrogen Peroxide; D010087:Oxides; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D000077191:Wortmannin; D051020:bcl-X Protein; C494811:BCL2L1 protein, human; C505407:CASP3 protein, human