Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma
Jelena Bošković,
Vladimir Dobričić,
Otilija Keta,
Lela Korićanac,
Jelena Žakula,
Jelena Dinić,
Sofija Jovanović Stojanov,
Aleksandar Pavić,
Olivera Čudina
Affiliations
Jelena Bošković
Department of Pharmaceutical Chemistry, University of Belgrade–Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
Vladimir Dobričić
Department of Pharmaceutical Chemistry, University of Belgrade–Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
Otilija Keta
Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovica Alasa 12-14, Vinca, 11351 Belgrade, Serbia
Lela Korićanac
Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovica Alasa 12-14, Vinca, 11351 Belgrade, Serbia
Jelena Žakula
Laboratory for Molecular Biology and Endocrinology, Vinča Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Petrovica Alasa 12-14, Vinca, 11351 Belgrade, Serbia
Jelena Dinić
Department of Neurobiology, Institute for Biological Research “Sinisa Stankovic”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia
Sofija Jovanović Stojanov
Department of Neurobiology, Institute for Biological Research “Sinisa Stankovic”, National Institute of the Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11108 Belgrade, Serbia
Aleksandar Pavić
Laboratory for Microbial Molecular Genetics and Ecology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia
Olivera Čudina
Department of Pharmaceutical Chemistry, University of Belgrade–Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia
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. IC50 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 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.
