title: Chemopreventive Properties of Genipin on AGS Cell Line via Induction of JNK/Nrf2/ARE Signaling Pathway.
abstract: Roles of dietary phytochemicals in cancer chemoprevention via induction of nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidant enzymes have been well established in a number of studies. In this study, FACS analysis was used to reveal that the intracellular reactive oxygen species level decreased at 0-25 μM of genipin treatment. Furthermore, immunofluorescence analysis and Western blotting were used to demonstrate that genipin treatment resulted in the upregulation and nuclear translocation of Nrf2, as well as upregulation of gastrointestinal glutathione peroxidase. Finally, we found that C-Jun-NH2-kinase (JNK) was also dose-dependently activated, where depleting JNK by using a biochemical inhibitor indicated that JNK was upstream of Nrf2. Interestingly, the antioxidant effects were limited to the treatment in the lower dosage of genipin, where higher dosage of genipin treatment resulted in the increased reactive oxygen species level and cytotoxicity. Thus, this study demonstrates for the first time that lower dosage of genipin results in the induction of JNK/Nrf2/ARE signaling pathway and protection from cell death.
authors.affiliation: College of Life Sciences & Biotechnology, Korea University, Seongbuk-gu, Seoul, Republic of Korea.
authors.forename: Jee Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Oncology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyeonseok
authors.initials: H
authors.lastname: Ko
authors.affiliation: College of Life Sciences & Biotechnology, Korea University, Seongbuk-gu, Seoul, Republic of Korea.
authors.forename: Sun-Joong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seongbuk-gu, Seoul, Republic of Korea.
authors.forename: So Hee
authors.initials: SH
authors.lastname: Shim
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Songpa-gu, Seoul, Republic of Korea.
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Ha
authors.affiliation: College of Life Sciences & Biotechnology, Korea University, Seongbuk-gu, Seoul, Republic of Korea.
authors.forename: Hyo Ihl
authors.initials: HI
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D039823:Iridoids / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism*
chemical_list: D016588:Anticarcinogenic Agents; D039823:Iridoids; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; C007834:genipin; D048031:JNK Mitogen-Activated Protein Kinases
keywords: AGS Cells; Genipin; JNK; Nrf2; Reactive Oxygen Species