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Activator Protein‐1 Mediates Docosahexaenoic Acid‐induced Apoptosis of Human Gastric Cancer Cells
Author(s) -
Lee Sun En,
Lim Joo Weon,
Kim Hyeyoung
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04716.x
Subject(s) - apoptosis , activator (genetics) , docosahexaenoic acid , cancer cell , kinase , cytochrome c , dna fragmentation , mapk/erk pathway , transfection , microbiology and biotechnology , biology , signal transduction , protein kinase a , chemistry , programmed cell death , cancer research , cancer , biochemistry , fatty acid , polyunsaturated fatty acid , gene , genetics
Docosahexaenoic acid (DHA) shows anti‐inflammatory and/or anticancer effects in some cells. Activator protein‐1 (AP‐1) regulates cellular proliferation and apoptosis. Although recent studies demonstrate the association between gastric cancer risk and DHA, the exact molecular mechanism has not been clarified. We investigated whether AP‐1 mediates DHA‐induced apoptosis of gastric cancer cells. We found that DHA induced cell death and DNA fragmentation in parallel with the activation of extracellular signal‐regulated kinases (ERK) and c‐Jun N‐terminal kinases (JNK) as well as AP‐1. DHA increased the protein levels of p53, cytochrome c , and Bax in gastric cancer cells. DHA‐induced DNA fragmentation and protein levels of p53, cytochrome c , and Bax were inhibited in the cells transfected with c‐jun dominant‐negative mutant (TAM67). Because JNK and ERK are upstream signaling for AP‐1 activation, we suggest that DHA‐induced activation of AP‐1 may mediate apoptosis of gastric cancer cells by inducing the expression of apoptotic genes in gastric cancer cells.