title: Reactive oxygen species-mediated activation of JNK and down-regulation of DAXX are critically involved in penta-O-galloyl-beta-d-glucose-induced apoptosis in chronic myeloid leukemia K562 cells.
abstract: Although 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG) was well known to have antitumor activities in breast, prostate, kidney, liver cancers and HL-60 leukemia via regulation of caspase 3, p53, S-phase kinase-associated protein 2 (Skp2) and insulin receptor signaling, the underlying mechanism of PGG-induced apoptosis linked with reactive oxygen species (ROS) mediated c-Jun N-terminal kinase (JNK) and DAXX was never elucidated in chronic myeloid leukemia (CML) K562 cells until now. Herein PGG significantly decreased the viability of CML cell lines such as K562 and KBM-5 without hurting normal peripheral blood lymphocytes (PBLs). PGG increased the number of TUNEL-positive cells and the sub-G1 cell population as well as activated caspase cascades including caspase-8, -9 and -3 in K562 cells. Interestingly, a significant activation of JNK by PGG was observed by MULTIPLEX assay and Western blotting. Conversely, JNK inhibitor D-JNKi suppressed the cleavages of caspase 3 and PARP induced by PGG in K562 cells. Also, PGG dramatically enhanced generation of ROS and reduced the expression of death-domain-associated protein (DAXX). Of note, ROS inhibitor acetyl-L-cysteine (NAC) reversed JNK-dependent apoptosis and DAXX inhibition induced by PGG. Overall, these findings suggest that ROS-dependent JNK activation and DAXX downregulation are critically involved in PGG-induced apoptosis in K562 cells.
authors: College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Tae-Rin
authors: TR
authors: Kwon
authors: Soo-Jin
authors: SJ
authors: Jeong
authors: Hyo-Jeong
authors: HJ
authors: Lee
authors: Hyo-Jung
authors: HJ
authors: Lee
authors: Eun Jung
authors: EJ
authors: Sohn
authors: Ji Hoon
authors: JH
authors: Jung
authors: Ji-Hyun
authors: JH
authors: Kim
authors: Deok-Beom
authors: DB
authors: Jung
authors: Junxaun
authors: J
authors: Lu
authors: Sung-Hoon
authors: SH
authors: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins; D015536:Down-Regulation; D004789:Enzyme Activation; D018922:HL-60 Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis*; D018832:Molecular Chaperones; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D047348:Hydrolyzable Tannins; D018832:Molecular Chaperones; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C435084:pentagalloylglucose; D048670:MAP Kinase Kinase 4; D020169:Caspases