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

Gökçe CİHAN-ÜSTÜNDAĞ; Berna SOMUNCU; Meltem MÜFTÜOĞLU; Nilgün KARALI

Makale detayları

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

Yazarlar:

Gökçe CİHAN-ÜSTÜNDAĞ | Berna SOMUNCU | Meltem MÜFTÜOĞLU | Nilgün KARALI

Yayıncı:

Istanbul University

Ana Başlıklar:

Farmakoloji ve terapötik

Dergi:

İstanbul Journal of Pharmacy 2021 Vol.51 Issue 2, pp.161-166

Belge Tipi:

Makale

Yayın Tarihi:

8/2021

Belge Dili:

İngilizce

Document ID (Org No.):

2000512821

Sıklık:

Aylık

eISSN:

2587-2087

Özet:

 

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 (APT) and 2D-NMR (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.

Makale detayları

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

Yazarlar: Gökçe CİHAN-ÜSTÜNDAĞ | Berna SOMUNCU | Meltem MÜFTÜOĞLU | Nilgün KARALI

Yayıncı: Istanbul University

Ana Başlıklar: Farmakoloji ve terapötik

Dergi: İstanbul Journal of Pharmacy 2021 Vol.51 Issue 2, pp.161-166

Belge Tipi: Makale

Yayın Tarihi: 8/2021

Belge Dili: İngilizce

Document ID (Org No.): 2000512821

Sıklık: Aylık

eISSN: 2587-2087

Sayı

Yazarlar:

Gökçe CİHAN-ÜSTÜNDAĞ | Berna SOMUNCU | Meltem MÜFTÜOĞLU | Nilgün KARALI

Yayıncı:

Istanbul University

Ana Başlıklar:

Farmakoloji ve terapötik

Dergi:

İstanbul Journal of Pharmacy 2021 Vol.51 Issue 2, pp.161-166

Belge Tipi:

Makale

Yayın Tarihi:

8/2021

Belge Dili:

İngilizce

Document ID (Org No.):

2000512821

Sıklık:

Aylık

eISSN:

2587-2087