Carcinogenesis Advance Access published online on June 3, 2004
Carcinogenesis, doi:10.1093/carcin/bgh199
© 2004 by Oxford University Press
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1 Department of Pathology, Dongguk University College of Medicine, Suek-jang Dong 707, Kyongju, Kyongbuk 780-714, Korea
* To whom correspondence should be addressed. E-mail: taejung{at}mail.dongguk.ac.kr.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are powerful chemopreventive agents in various cancers. They act by inhibiting cyclooxygenase (COX) activity, or through other mechanisms. NSAID activated gene (NAG-1) has antitumorigenic and proapoptotic activities, but the mechanisms of NAG-1 induced apoptosis are poorly understood. Here we examined whether NAG-1 expression is induced in gastric cancer cells treated with NSAIDs, and the effect of NAG-1 expression on cell death. NAG-1 cDNA was transfected into SNU601 cells, and the relation between the ectopic expression of NAG-1 and death receptor-4 (DR-4) and DR-5 levels was studied. We found that NAG-1 expression was strongly induced in SNU601 cells, which lack endogenous cyclooxygenase-2, by sulindac sulfide, and that this was closely related with increased apoptosis and decreased cell viability. Moreover, temporal expressions of DR-4 and DR-5 induced by sulindac sulfide were similar to that of NAG-1. Most SNU601 cells transfected with NAG-1 cDNA did not survive during expansion. Forced NAG-1 expression significantly induced apoptosis and DR-4 and DR-5 expression. We conclude that NAG-1 expression is closely related to DR-4 and DR-5 induction, which could provide a mechanistic basis for the apoptotic effect of cyclooxygenase inhibitors in gastric cancer cells. Key Words:
NAG-1, nonsteroidal anti-inflammatory drug, apoptosis, death receptor, gastric cancer
Revised May 11, 2004
Accepted May 25, 2004
CANCER BIOLOGY
Nonsteroidal anti-inflammatory drug activated gene (NAG-1) expression is closely related to death receptor-4 and -5 induction, which may explain sulindac sulfide-induced gastric cancer cell apoptosis
2 Department of Gastroenterology, Dongguk University College of Medicine, Suek-jang Dong 707, Kyongju, Kyongbuk 780-714, Korea
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