Anti-inflammatory effects of indomethacin's methyl ester derivative and induction of apoptosis in HL-60 cells

Su Hui Chao, An-Bang Wu, Chia Jung Lee, Fu An Chen, Ching Chiung Wang

研究成果: 雜誌貢獻文章同行評審

8 引文 斯高帕斯(Scopus)

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.
原文英語
頁(從 - 到)2206-2210
頁數5
期刊Biological and Pharmaceutical Bulletin
28
發行號12
DOIs
出版狀態已發佈 - 十二月 2005

ASJC Scopus subject areas

  • 藥理
  • 藥學科學

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