title: Pachymic Acid Induces Apoptosis of EJ Bladder Cancer Cells by DR5 Up-Regulation, ROS Generation, Modulation of Bcl-2 and IAP Family Members.
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.
authors.affiliation: Departments of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, Republic of Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, 660-702, Republic of Korea.
authors.forename: Won Sup
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, 660-702, Republic of Korea.
authors.forename: Se-Il
authors.initials: SI
authors.lastname: Go
authors.affiliation: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, 660-702, Republic of Korea.
authors.forename: Arulkumar
authors.initials: A
authors.lastname: Nagappan
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Baek
authors.affiliation: Department of Microbiology, College of Natural Sciences, Pusan National University, Busan, 609-735, Republic of Korea.
authors.forename: Jae-Dong
authors.initials: JD
authors.lastname: Lee
authors.affiliation: Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Marine Life Sciences, Jeju National University, Jeju, 690-756, Republic of Korea.
authors.forename: Gi Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, 660-702, Republic of Korea.
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: School of Veterinary Medicine, Geongsang National University, Jinju, Republic of Korea.
authors.forename: Gon-Sup
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Department of Immunology, School of Medicine, Keimyung University, Daegu, 704-701, Republic of Korea.
authors.forename: Taeg Kyu
authors.initials: TK
authors.lastname: Kwon
authors.affiliation: Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Chung Ho
authors.initials: CH
authors.lastname: Ryu
authors.affiliation: Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Sung Chul
authors.initials: SC
authors.lastname: Shin
authors.affiliation: Departments of Biochemistry, Dongeui University College of Korean Medicine, Busan, 614-052, Republic of Korea.|Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, Busan, 614-714, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D015536:Down-Regulation; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014315:Triterpenes; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D010741:Phospholipases A; D053148:Caspase 3; D020169:Caspases; D000111:Acetylcysteine; C102487:pachymic acid
keywords: EJ bladder cancer cells; apoptosis; caspase; death receptor; pachymic acid; reactive oxygen species