title: Naringenin causes ASK1-induced apoptosis via reactive oxygen species in human pancreatic cancer cells.
abstract: Naringenin, one of the most abundant flavonoids in natural citrus fruits, has been investigated for its ability to inhibit growth of breast, colon, gastric and prostate cancer cells. However, naringenin-induced cell death in pancreatic cancer is not well understood. Therefore, we analyzed the naringenin-induced apoptosis mechanism using human pancreatic cancer SNU-213 cells. Annexin V+/PI + marked cells increased from 5.10% to 8.29%, 25.06% and 35.31% in response to treatment with 200, 400, and 600 μM naringenin, respectively. Two-dimensional electrophoresis to identify possible target-related proteins of naringenin-induced apoptosis revealed seven proteins. Among these, the expression of peroxiredoxin-1 (Prdx-1), which modulates redox homeostasis of cells, was decreased. To obtain a broad understanding of the interactive mechanism of naringenin and Prdx-1, we observed changes in reactive oxygen species (ROS) in naringenin-treated SNU-213 cells. The ROS levels were 130.02 ± 20.21%, 182.04 ± 5.39%, and 237.21 ± 12.71% in response to 200, 400, and 600 μM naringenin treatment, respectively. Increases in ROS were followed by up-regulation of apoptosis signal-regulation kinase 1 (ASK1). Moreover, the JNK, p38 and p53 proteins were upregulated. Overall, the results of this study suggest that naringenin causes ASK1-induced apoptosis mediated by ROS.
authors.affiliation: Department of Biological Science, Gachon University, Seongnam, 461-701, Republic of Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Biological Science, Gachon University, Seongnam, 461-701, Republic of Korea.
authors.forename: Yong Jun
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Biological Science, Gachon University, Seongnam, 461-701, Republic of Korea.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Gachon University, Seongnam, 461-701, Republic of Korea. Electronic address: genetx@hanmail.net.
authors.forename: Myeong Jin
authors.initials: MJ
authors.lastname: Nam
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004965:Estrogen Antagonists / Q000494:pharmacology*; D044950:Flavanones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D044950:Flavanones; D010446:Peptide Fragments; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C509415:p53 protein (325-355), human; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; C005273:naringenin
keywords: Apoptosis signal-regulation kinase 1; Naringenin; Pancreatic cancer; Peroxiredoxin-1; Reactive oxygen species