title: Activator protein-1 mediates docosahexaenoic acid-induced apoptosis of human gastric cancer cells.
abstract: 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.
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Sun En
authors.initials: SE
authors.lastname: Lee
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D010446:Peptide Fragments; D016755:Proto-Oncogene Proteins c-jun; C439528:TAM67 peptide; C495901:TP53 protein, human; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004281:Docosahexaenoic Acids; D045304:Cytochromes c; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases