Genistein induces apoptosis in T lymphoma cells via mitochondrial damage

被引:51
作者
Baxa, DM
Luo, XX
Yoshimura, FK
机构
[1] Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA
[2] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA
[3] Henry Ford Hlth Syst, Infect Dis Res, Detroit, MI 48202 USA
来源
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL | 2005年 / 51卷 / 01期
关键词
D O I
10.1207/s15327914nc5101_13
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The soy isoflavone genistein has been identified as having antiproliferative and apoptotic effects on various malignant cell types derived from solid tumors. Because little information regarding the effect of genistein on hematopoietic malignancies is available, we undertook this study of T-cell lymphomas. We tested the effect of genistein on murine T-cell lines derived from thymic lymphomas induced by an oncogenic murine leukemia virus. When T lymphoma cells were treated with genistein concentrations of 15 mu M and greater it was observed that the percentage of viable cells was significantly reduced in a dose- and time-dependent manner The observed cell killing was found to be the result of apoptosis as detected by flow cytometric analysis of cells stained with annexin V and propidium iodide and assays for caspase-3 activation and DNA fragmentation. Cell staining with the mitochondrial specific dye JC-1 and detection of caspase-9 activation revealed that genistein produced mitochondrial depolarization as an early step in the induction of apoptosis. Bongkrekic acid inhibition of mitochondrial depolarization identified the mitochondria permeability transition pore (PTP) as a potential target of genistein activity. These results indicate that the induction of apoptosis by pharmacological concentrations of genistein in T lymphoma cells occurs via mitochondrial damage with the involvement of the PTP.
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页码:93 / 101
页数:9
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