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Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members

Title
Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members
Author
이수재
Keywords
pachymic acid; EJ bladder cancer cells; apoptosis; death receptor; caspase; reactive oxygen species
Issue Date
2015-10
Publisher
WILEY-BLACKWELL
Citation
PHYTOTHERAPY RESEARCH, v. 29, NO 10, Page. 1516-1524
Abstract
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 (Delta Psi(m)) 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. Copyright (c) 2015 John Wiley & Sons, Ltd.
URI
http://onlinelibrary.wiley.com/doi/10.1002/ptr.5402/abstract?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+12th+August+at+3%3A00+EDT+%2F+8%3A00+BST+%2F+12%3A30+IST+%2F+15%3A00+SGT+for+4+hours+for+essential+maintenance.+Apologies+for+the+inconvenience.http://hdl.handle.net/20.500.11754/28443
ISSN
0951-418X; 1099-1573
DOI
10.1002/ptr.5402
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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