细胞色素c
DNA断裂
细胞凋亡
茶黄素
化学
生物化学
分子生物学
聚ADP核糖聚合酶
半胱氨酸蛋白酶3
程序性细胞死亡
生物
多酚
DNA
聚合酶
抗氧化剂
作者
Min‐Hsiung Pan,Yu Chih Liang,Shoei‐Yn Lin‐Shiau,Nan Zhu,Chi Tang Ho,Ju‐Li Lin
摘要
This study examined the growth inhibitory effects of theasinensin A (from oolong tea) and black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate (TF-2a) and theaflavin-3‘-gallate (TF-2b), and theaflavin-3,3‘-digallate (TF-3) in human cancer cells. Theasinensin A, TF-1, and TF-2 displayed strong growth inhibitory effects against human histolytic lymphoma U937, with estimated IC50 values of 12 μM, but were less effective against human acute T cell leukemia Jurkat, whereas TF-3 and (−)-epigallocatechin-3-gallate (EGCG) had lower activities. The molecular mechanisms of tea polyphenol-induced apoptosis as determined by annexin V apoptosis assay, DNA fragmentation, and caspase activation were further investigated. Loss of membrane potential and reactive oxygen species (ROS) generation were also detected by flow cytometry. Treatment with tea polyphenols caused rapid induction of caspase-3, but not caspase-1, activity and stimulated proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Pretreatment with a potent caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone, inhibited theasinensin A induced DNA fragmentation. Furthermore, it was found that theasinensin A induced loss of mitochondrial transmembrane potential, elevation of ROS production, release of mitochondrial cytochrome c into the cytosol, and subsequent induction of caspase-9 activity. These results indicate that theasinensin A allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA and induces DFF-45 (DNA fragmentation factor) degradation. The results suggest that induction of apoptosis by theasinensin A may provide a pivotal mechanism for their cancer chemopreventive function. Keywords: Apoptosis; oolong tea; theasinensin A; caspase; U937 cells
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