Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up‐Regulation,ROS Generation,Modulation of Bcl‐2 and IAP Family Members |
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| Authors: | Jin‐Woo Jeong Won Sup Lee Se‐il Go Arulkumar Nagappan Jun Young Baek Jae‐Dong Lee Su‐Jae Lee Cheol Park Gi Young Kim Hye Jung Kim Gon‐Sup Kim Taeg Kyu Kwon Chung Ho Ryu Sung Chul Shin Yung Hyun Choi |
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| Institution: | 1. Departments of Biochemistry, Dongeui University College of Korean Medicine, Busan, Republic of Korea;2. Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;3. Department of Microbiology, College of Natural Sciences, Pusan National University, Busan, Republic of Korea;4. Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Republic of Korea;5. Department of Molecular Biology, Dongeui University, Busan, Republic of Korea;6. Department of Marine Life Sciences, Jeju National University, Jeju, Republic of Korea;7. Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Republic of Korea;8. School of Veterinary Medicine, Geongsang National University, Jinju, Republic of Korea;9. Department of Immunology, School of Medicine, Keimyung University, Daegu, Republic of Korea;10. Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Republic of Korea;11. Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea;12. Anti‐Aging Research Center and Blue‐Bio Industry RIC, Dongeui University, Busan, Republic of Korea |
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| 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 (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. Copyright © 2015 John Wiley & Sons, Ltd. |
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| Keywords: | pachymic acid EJ bladder cancer cells apoptosis death receptor caspase reactive oxygen species |
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