Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene

✍ Scribed by Jeong Hong Kim; Jung Hyun Chang; Kwang-Hyeon Rhee; Joo-Heon Yoon; Soon Ho Kwon; Keejae Song; Kun Wayn Lee; Chang Il Cho; Ju Hyun Jeon; Kyung-Su Kim

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 430 KB
• Volume: 122
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.23302

✦ Synopsis

Abstract

Nonsteroidal anti‐inflammatory drug‐activated gene‐1 (NAG‐1) has recently been shown to be induced by nonsteroidal anti‐inflammatory drugs (NSAIDs) and to have proapoptotic and antitumorigenic activities. Although sulindac sulfide induced apoptosis in sinonasal cancer cells, the relationship between NAG‐1 and NSAIDs has not been determined. In this study, we investigated the induction of apoptosis in sinonasal cancer cells treated by various NSAIDs and the role of NAG‐1 expression in this induction. The effect of NSAIDs on normal human nasal epithelial (NHNE) cells was also examined to evaluate their safety on normal cells. Finally, the in vivo anti‐tumorigenic activity of NSAIDs in mice was investigated. In AMC‐HN5 human sinonasal carcinoma cells, indomethacin was the most potent NAG‐1 inducer and caused NAG‐1 expression in a time‐ and dose‐dependent manner. The induction of NAG‐1 expression preceded the induction of apoptosis. Conditioned medium from NAG‐1‐overexpressing Drosophila cells inhibited proliferation of sinonasal cancer cells and induced apoptosis. In addition, in NAG‐1 small interfering RNA‐transfected cells, apoptosis induced by indomethacin was suppressed. In contrast, NAG‐1 expression and apoptosis were not induced by NSAIDs or conditioned medium in NHNE cells. Furthermore, indomethacin induced a dose‐dependent in vivo increase in the expression of NAG‐1 mRNA in the mice tumors and the volume of xenograft tumors of AMC‐HN5 cells in indomethacin‐treated nude mice was reduced compared to that in control mice. In conclusion, indomethacin exerts proapoptotic and antitumorigenic effects in sinonasal cancer cells through the induction of NAG‐1 and can be considered a safe and effective chemopreventive agent against sinonasal cancer. © 2007 Wiley‐Liss, Inc.