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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
Author(s) -
Jeong JinWoo,
Lee Won Sup,
Go Seil,
Nagappan Arulkumar,
Baek Jun Young,
Lee JaeDong,
Lee SuJae,
Park Cheol,
Kim Gi Young,
Kim Hye Jung,
Kim GonSup,
Kwon Taeg Kyu,
Ryu Chung Ho,
Shin Sung Chul,
Choi Yung Hyun
Publication year - 2015
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5402
Subject(s) - apoptosis , cytochrome c , reactive oxygen species , dna fragmentation , cancer cell , biology , population , dna laddering , programmed cell death , microbiology and biotechnology , chemistry , biochemistry , cancer , medicine , genetics , environmental health
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 (ΔΨ 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 © 2015 John Wiley & Sons, Ltd.