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Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma.

Authors :
Bošković J
Dobričić V
Keta O
Korićanac L
Žakula J
Dinić J
Jovanović Stojanov S
Pavić A
Čudina O
Source :
Pharmaceutics [Pharmaceutics] 2024 Jun 18; Vol. 16 (6). Date of Electronic Publication: 2024 Jun 18.
Publication Year :
2024

Abstract

Apart from cytotoxicity, inhibitors of the COX-2 enzyme have demonstrated additional effects important for cancer treatment (such as radiosensitization of tumor cells and cell antimigratory effects); however, the relationship between the inhibition of other inflammation-related enzyme 5-LOX inhibitors and anticancer activity is still not well understood. In our study, the cytotoxicity of thirteen COX-2 and 5-LOX inhibitors previously presented by our group ( 1 - 13 ) was tested on three cancer cell lines (HCT 116, HT-29 and BxPC-3) and one healthy cell line (MRC-5). Compounds 3 , 5 , 6 and 7 showed moderate cytotoxicity, but good selectivity towards cancer cell lines. IC <subscript>50</subscript> values were in the range of 22.99-51.66 µM (HCT 116 cell line), 8.63-41.20 µM (BxPC-3 cell line) and 24.78-81.60 µM (HT-29 cell line; compound 7 > 100 µM). In comparison to tested, commercially available COX-2 and 5-LOX inhibitors, both cytotoxicity and selectivity were increased. The addition of compounds 6 and 7 to irradiation treatment showed the most significant decrease in cell proliferation of the HT-29 cell line ( p < 0.001). The antimigratory potential of the best dual COX-2 and 5-LOX inhibitors (compounds 1 , 2 , 3 and 5 ) was tested by a wound-healing assay using the SW620 cell line. Compounds 1 and 3 were singled out as compounds with the most potent effect (relative wound closure was 3.20% (24 h), 5,08% (48 h) for compound 1 and 3.86% (24 h), 7.68% (48 h) for compound 3 ). Considering all these results, compound 3 stood out as the compound with the most optimal biological activity, with the best dual COX-2 and 5-LOX inhibitory activity, good selectivity towards tested cancer cell lines, significant cell antimigratory potential and a lack of toxic effects at therapeutic doses.

Details

Language :
English
ISSN :
1999-4923
Volume :
16
Issue :
6
Database :
MEDLINE
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
38931946
Full Text :
https://doi.org/10.3390/pharmaceutics16060826