Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members
- Authors
- Jeong, Jin-Woo; Lee, Won Sup; Go, Se-il; Nagappan, Arulkumar; Baek, Jun Young; Lee, Jae-Dong; Lee, Su-Jae; Park, Cheol; Kim, Gi Young; Kim, Hye Jung; Kim, Gon-Sup; Kwon, Taeg Kyu; Ryu, Chung Ho; Shin, Sung Chul; Choi, Yung Hyun
- Issue Date
- Oct-2015
- Publisher
- WILEY-BLACKWELL
- Keywords
- pachymic acid; EJ bladder cancer cells; apoptosis; death receptor; caspase; reactive oxygen species
- Citation
- PHYTOTHERAPY RESEARCH, v.29, no.10, pp.1516 - 1524
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHYTOTHERAPY RESEARCH
- Volume
- 29
- Number
- 10
- Start Page
- 1516
- End Page
- 1524
- URI
- https://scholarworks.bwise.kr/gnu/handle/sw.gnu/16984
- DOI
- 10.1002/ptr.5402
- ISSN
- 0951-418X
- 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.
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Collections - 농업생명과학대학 > 식품공학부 > Journal Articles
- 수의과대학 > Department of Veterinary Medicine > Journal Articles
- College of Medicine > Department of Medicine > Journal Articles
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