细胞凋亡
细胞色素c
活性氧
DNA断裂
癌细胞
人口
DNA梯
生物
化学
程序性细胞死亡
分子生物学
细胞生物学
生物化学
癌症
医学
环境卫生
遗传学
作者
Jin Woo Jeong,Won Sup Lee,Se Il Go,Arulkumar Nagappan,Jun Young Baek,Jae Dong Lee,Su Jae Lee,Cheol Park,Jin Chul Kim,Hye Jung Kim,Gon Sup Kim,Taeg Kyu Kwon,Chung Ho Ryu,Sung Chul Shin,Yung Hyun Choi
摘要
Pachymic acid (PA) is a lanostane-type triterpenoid derived from Poria cocos mushroom that possess various biological effects such as anti-cancer, antiinflammatory and anti-metastasis effects. In this study, we investigated the anti-cancer effects of PA in EJ bladder cancer cells. The results showed that PA significantly inhibited proliferation of EJ cells in a dose-dependent manner. PA induced accumulation of sub-G1 DNA content (apoptotic cell population), apoptotic bodies and chromatin condensation and DNA fragmentation in EJ cells in a dose-dependent manner. PA also induces activation of caspase-3, -8 and -9, and subsequent cleavage of poly (ADP-ribose) polymerase, and significantly suppressed the inhibitor of apoptosis protein family proteins in a dose-dependent manner. Furthermore, PA activates Bid and induced the loss of mitochondrial membrane potential (ΔΨm ) with up-regulated pro-apoptotic proteins (Bax and Bad), down-regulated anti-apoptotic proteins (Bcl-2 and Bcl-xL) and cytochrome c release. In turn, PA increased the generation of reactive oxygen species (ROS); also, the ROS production was blocked by N-acetyl-L-cysteine. The expressions of TNF-related apoptosis inducing ligand and death receptor 5 were up-regulated by PA in a dose-dependent manner, suggesting extrinsic pathway also involved in PA-induced apoptosis. This study provides evidence that PA might be useful in the treatment of human bladder cancer.
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