Nutrition & Cancer, 2005, 51(1):93.

Genistein induces apoptosis in T lymphoma cells via mitochondrial damage

Dwayne M. Baxa, Xixia Luo, Fayth K. Yoshimura

Infectious Disease Research, Henry Ford Health System, Detroit, MI 48202, USA; et al

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 microM 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.

美国《营养与癌症》，2005年

金雀异黄素通过线粒体损伤诱导T淋巴细胞凋亡

戴维尼 M 巴萨，罗喜霞，等

传染病研究，亨利·福特健康系统，底特律，MI 48202，美国；等

大豆异黄酮染料木黄酮已经被鉴定为对来自实体瘤的各种恶性细胞类型具有抗增殖和凋亡作用。因为关于染料木素对造血恶性肿瘤的影响的少量信息可用，我们进行了这项对T细胞淋巴瘤的研究。我们测试了染料木素对由致癌鼠白血病病毒诱导的胸腺淋巴瘤衍生的鼠T细胞系的影响。当T淋巴瘤细胞用15微米或更大的染料木素浓度处理时，观察到活细胞的百分比以剂量和时间依赖性方式显着降低。发现观察到的细胞杀伤是通过用膜联蛋白V和碘化丙啶染色的细胞的流式细胞术分析和胱天蛋白酶-3激活和DNA断裂测定法检测的细胞凋亡的结果。用线粒体特异性染料JC-1细胞染色和胱天蛋白酶-9活化的检测显示，染料木黄酮产生线粒体去极化作为凋亡诱导的早期步骤。线粒体去极化的Bongkrekic酸抑制将线粒体通透性转换孔（PTP）鉴定为染料木黄酮活性的潜在靶标。这些结果表明，T淋巴瘤细胞中染料木黄酮的药理学浓度诱导细胞凋亡通过PTP参与的线粒体损伤发生。