| Cyclooxygenase inhibitors induce apoptosis in sinonasal cancer cells by increased expression of nonsteroidal anti-inflammatory drug-activated gene. | |
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MedLine Citation:
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PMID: 18076062 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 122 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-02-25 Completed Date: 2008-03-06 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 1765-73 Citation Subset: IM |
Affiliation:
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Department of Otorhinolaryngology, Cheju National University College of Medicine, Jeju, South Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology* Antineoplastic Agents / pharmacology* Apoptosis / drug effects Blotting, Western Carcinoma / drug therapy*, metabolism, pathology Cell Line, Tumor Cell Proliferation / drug effects Cyclooxygenase Inhibitors / pharmacology* Cytokines / drug effects, genetics, metabolism* Dose-Response Relationship, Drug Flow Cytometry Gene Expression Regulation, Neoplastic / drug effects Growth Differentiation Factor 15 Humans Indomethacin / pharmacology* Mice Mice, Nude Paranasal Sinus Neoplasms / drug therapy*, metabolism, pathology RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Time Factors Transfection Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antineoplastic Agents; 0/Cyclooxygenase Inhibitors; 0/Cytokines; 0/GDF15 protein, human; 0/Gdf15 protein, mouse; 0/Growth Differentiation Factor 15; 0/RNA, Small Interfering; 53-86-1/Indomethacin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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