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

Bošković, Jelena; Dobričić, Vladimir; Keta, Otilija; Korićanac, Lela; Žakula, Jelena; Dinić, Jelena; Jovanović Stojanov, Sofija; Pavić, Aleksandar; Čudina, Olivera

doi:10.3390/pharmaceutics16060826

Open AccessArticle

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

by

Jelena Bošković

¹,

Vladimir Dobričić

^1,*

,

Otilija Keta

²

,

Lela Korićanac

²,

Jelena Žakula

²,

Jelena Dinić

³

,

Sofija Jovanović Stojanov

³

,

Aleksandar Pavić

⁴

and

Olivera Čudina

¹

Department of Pharmaceutical Chemistry, University of Belgrade–Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia

²

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

³

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

⁴

Laboratory for Microbial Molecular Genetics and Ecology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444a, 11000 Belgrade, Serbia

^*

Author to whom correspondence should be addressed.

Pharmaceutics 2024, 16(6), 826; https://doi.org/10.3390/pharmaceutics16060826

Submission received: 3 May 2024 / Revised: 7 June 2024 / Accepted: 10 June 2024 / Published: 18 June 2024

(This article belongs to the Special Issue Studies on the Cytotoxicity and Antimicrobial Effects of Synthetic and Natural Compounds)

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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. 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 < 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.

Keywords: COX-2; 5-LOX; synthesis; cytotoxicity; radiosensitization; antimigratory potential; toxicity

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MDPI and ACS Style

Bošković, J.; Dobričić, V.; Keta, O.; Korićanac, L.; Žakula, J.; Dinić, J.; Jovanović Stojanov, S.; Pavić, A.; Čudina, O. Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma. Pharmaceutics 2024, 16, 826. https://doi.org/10.3390/pharmaceutics16060826

AMA Style

Bošković J, Dobričić V, Keta O, Korićanac L, Žakula J, Dinić J, Jovanović Stojanov S, Pavić A, Čudina O. Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma. Pharmaceutics. 2024; 16(6):826. https://doi.org/10.3390/pharmaceutics16060826

Chicago/Turabian Style

Bošković, Jelena, Vladimir Dobričić, Otilija Keta, Lela Korićanac, Jelena Žakula, Jelena Dinić, Sofija Jovanović Stojanov, Aleksandar Pavić, and Olivera Čudina. 2024. "Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma" Pharmaceutics 16, no. 6: 826. https://doi.org/10.3390/pharmaceutics16060826

APA Style

Bošković, J., Dobričić, V., Keta, O., Korićanac, L., Žakula, J., Dinić, J., Jovanović Stojanov, S., Pavić, A., & Čudina, O. (2024). Unveiling Anticancer Potential of COX-2 and 5-LOX Inhibitors: Cytotoxicity, Radiosensitization Potential and Antimigratory Activity against Colorectal and Pancreatic Carcinoma. Pharmaceutics, 16(6), 826. https://doi.org/10.3390/pharmaceutics16060826

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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

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