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标题：Anti-inflammatory Effects of Indomethacin's Methyl Ester Derivative and Induction of Apoptosis in HL-60 Cells
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作者：Su-Hui Chao ; An-Bang Wu ; Chia-Jung Lee 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2005
卷号：28
期号：12
页码：2206-2210
DOI：10.1248/bpb.28.2206
出版社：The Pharmaceutical Society of Japan
摘要：Indomethacin is used as an anti-inflammatory drug and a nonselective cyclooxygenase inhibitor. When indomethacin in methanol was photo-irradiated with an Hg lamp, methyl ester, ethyl ester, and γ-lactone derivatives of indomethacin were produced. In the present study, we found that the methyl ester derivative of indomethacin (M-IN) could more potently inhibit prostaglandin E₂ (PGE₂) and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX 2) protein expression from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than indomethacin, similar to the effect of a non-steroidal anti-inflammatory drugs (NSAID). On the other hand, the results showed that M-IN with an IC₅₀ value maintained at 36.9 μg/ml for 12 h exhibited stronger cytotoxicity than ethyl ester, γ-lactone derivatives of indomethacin, and indomethacin in promyelocytic leukemia HL-60 cells. Moreover, a series of biochemical analyses determined that M-IN caused apoptotic bodies, DNA fragmentation, and enhanced PARP and pro-caspase 3 degradation in HL-60 cells. These above results indicate that the photosynthesized product, M-IN, had stronger anti-inflammatory effects in LPS-stimulated RAW 264.7 cells and cytotoxicity effects in HL-60 cells than the parent drug, indomethacin.
关键词：anti-inflammatory drug;cyclooxygenase;apoptosis;caspase 3;[1-(4-chloro-benzoyl)-5-methoxy-2-methyl-indol-3-yl]-acetic acid methyl ester