Nakazato Tomonori, Ito Keisuke, Miyakawa Yoshitaka, Kinjo Kentaro, Yamada Taketo, Hozumi Nobumichi, Ikeda Yasuo, Kizaki Masahiro
Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Haematologica. 2005 Mar;90(3):317-25.
The aim of this study was to investigate the possibility of green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG) as a novel therapeutic agent for the patients with myeloid leukemia.
We investigated the effects of EGCG on the induction of apoptosis in leukemic cells in vitro and in vivo. We further examined the molecular mechanisms of EGCG-induced apoptosis in myeloid leukemic cells.
EGCG rapidly induced apoptotic cell death in retinoic acid (RA)-resistant acute promyelocytic leukemia (APL), UF-1 cells within 3 h. EGCG induced apoptosis in UF-1 cells was in association with the loss of mitochondrial transmembrane potentials (Deltapsim) and activation of caspase-3 and -9. Elevation of intracellular reactive oxygen species (ROS) production was also demonstrated during EGCG-induced apoptosis of UF-1 as well as fresh myeloid leukemic cells. In NOD/SCID mice transplanted with UF-1 cells, EGCG effectively inhibited tumor growth in vivo, and the number of mitoses among the cells significantly decreased in comparison to that of control mouse cells.
In summary, EGCG has potential as a novel therapeutic agent for myeloid leukemia via induction of apoptosis mediated by modification of the redox system.
本研究旨在探讨绿茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）作为髓系白血病患者新型治疗药物的可能性。
我们研究了EGCG在体外和体内对白血病细胞凋亡诱导的影响。我们还进一步研究了EGCG诱导髓系白血病细胞凋亡的分子机制。
EGCG在3小时内迅速诱导视黄酸（RA）耐药的急性早幼粒细胞白血病（APL）UF-1细胞发生凋亡性细胞死亡。EGCG诱导UF-1细胞凋亡与线粒体跨膜电位（Δψm）丧失以及半胱天冬酶-3和-9的激活有关。在EGCG诱导UF-1细胞以及新鲜髓系白血病细胞凋亡过程中，还证实细胞内活性氧（ROS）生成增加。在移植了UF-1细胞的NOD/SCID小鼠中，EGCG在体内有效抑制肿瘤生长，与对照小鼠细胞相比，细胞中的有丝分裂数量显著减少。
总之，EGCG有潜力通过诱导由氧化还原系统修饰介导的凋亡，成为髓系白血病的新型治疗药物。
