TY - GEN
T1 - Activator protein-1 mediates docosahexaenoic acid-induced apoptosis of human gastric cancer cells
AU - Lee, Sun En
AU - Lim, Joo Weon
AU - Kim, Hyeyoung
PY - 2009/8
Y1 - 2009/8
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1749-6632.2009.04716.x
DO - 10.1111/j.1749-6632.2009.04716.x
M3 - Conference contribution
C2 - 19723051
AN - SCOPUS:69149090288
SN - 9781573317375
T3 - Annals of the New York Academy of Sciences
SP - 163
EP - 169
BT - Natural Compounds and Their Role in Apoptotic Cell Signaling Pathways
PB - Blackwell Publishing Inc.
ER -
