Anti-proliferative effects of indomethacin, acemetacin and their tromethamine salts in HCT116 human colon cancer cells

Authors : Gökçe CİHANÜSTÜNDAĞ, Berna SOMUNCU, Meltem MÜFTÜOĞLU, Nilgün KARALI

Pages : 161-166

View : 41 | Download : 10

Publication Date : 2021-08-31

Article Type : Research Paper

Abstract :Background and Aims: Since 1980`s, several preclinical studies have been published on the anti-colorectal cancer activity of the nonsteroidal anti-inflammatory drug indomethacin. The direct anti-proliferative effect of indomethacin seems to occur via a variety of reported COX-independent mechanisms. Acemetacin is a glycolic acid ester derivative of indomethacin and contrary to indomethacin, there is not much published research on anti-cancer effects of acemetacin. Herein, we compared the in vitro anti-proliferative properties of indomethacin, acemetacin, and their tromethamine salts in HCT116 colon cancer cells. Methods: The tromethamine salts of indomethacin and acemetacin were synthesized and the structures were established by microanalysis, IR, 1H-NMR, 13C-NMR insert ignore into journalissuearticles values(APT); and 2D-NMR insert ignore into journalissuearticles values(HSQC and HMBC); spectrometry. Cell proliferation assays were performed using xCELLigence real-time cell analysis system. Results: Indomethacin exhibited profound inhibitory effects with IC50 values at low micromolar ranges. Acemetacin exhibited far lower cytotoxic activity as compared to that of indomethacin. Surprisingly, indomethacin-tromethamine salt was 2-fold and 4.4-fold more potent than indomethacin at 48 and 72 h, respectively, while maintaining its activity at 24 h. The tromethamine salt of acemetacin was more potent than acemetacin at 24 h and 48 h post-treatment. Conclusion: The anti-proliferative effect of indomethacin in HCT116 cells was found to be at low micro-molar levels. The esterification of indomethacin with glycolic acid caused a strong decrease in anti-proliferative effect. The salt formation caused a positive effect on the anti-proliferative activity of indomethacin and indomethacin-tromethamine salt may be a promising candidate for additional in vivo studies.
Keywords : indomethacin, acemetacin, tromethamine, HCT116, anti cancer

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