Hydrogen peroxide in the Burkitt's lymphoma cell line Raji provides protection against arsenic trioxide-induced apoptosis via the phosphoinositide-3 kinase signalling pathway

被引:13
作者
Lu, D
Bai, XC
Gui, L
Su, YC
Deng, F
Liu, B
Li, XM
Zeng, WS
Cheng, BL
Luo, SQ [1 ]
机构
[1] First Mil Med Univ, Dept Cell Biol, Guangzhou 510515, Peoples R China
[2] Kunming Med Coll, Dept Anat, Kunming, Peoples R China
[3] Kunming Railway Hosp, Dept Endocrinol, Kunming, Peoples R China
[4] First Mil Med Univ, Dept Med Phys, Guangzhou 510515, Peoples R China
[5] Nangfang Hosp, Dept Orthopaed & Spinal Surg, Guangzhou, Peoples R China
关键词
hydrogen peroxide; arsenic trioxide; apoptosis; phosphoinositide-3; kinase; signal transduction;
D O I
10.1111/j.1365-2141.2004.04940.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We on arsenic trioxide examined the effects of hydrogen peroxide (H2O2) (As2O3)-induced cell killing. Low concentrations of H2O2 (200 mumol/l) inhibited the ability of As2O3 to induce apoptosis in the Burkitt's lymphoma cell line Raji. H2O2 altered the form of cell death from apoptosis to pyknosis/ necrosis and also lowered the degree of cell killing by As2O3. H2O2 was capable of preventing caspase-3 activation induced by As2O3 in Raji cells. Incubation of cells with a phosphoinositide-3 kinase (PI-3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H2O2 on As2O3-induced caspase-3 activation. In addition, the PI-3K inhibitor partially blocked the effects of H2O2 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 H2O2 provide protection against the in vivo of As2O3-induced apoptosis. PI-3K plays a crucial role in enhancing cell survival during H2O2, inhibiting As2O3-induced apoptosis in the Burkitt's lymphoma cells. As2O3-induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol.
引用
收藏
页码:512 / 520
页数:9
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