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Chemopreventive Properties of Genipin on AGS Cell Line via Induction of JNK/Nrf2/ARE Signaling Pathway
Author(s) -
Kim Jee Min,
Ko Hyeonseok,
Kim SunJoong,
Shim So Hee,
Ha Chang Hoon,
Chang Hyo Ihl
Publication year - 2016
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21741
Subject(s) - genipin , downregulation and upregulation , reactive oxygen species , chemistry , antioxidant , glutathione , signal transduction , pharmacology , biochemistry , biology , enzyme , chitosan , gene
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.