Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolites
such as inflammatory mediators—prostaglandins and leukotrienes. The inhibition of lipoxygenases
is increasingly employed in the treatment of cancer. We evaluated the anticancer potential of two
novel 5-lipoxygenase inhibitors, named CarbZDNaph and CarbZDChin, which are analogues of
the commercially available inhibitor Rev-5901. The in vitro segment of this study was conducted
on a mouse colorectal carcinoma cell line—CT26CL25. For an in vivo model, we induced tumors
in BALB/c mice by the implantation of CT26CL25 cells, and we treated the animals with potential
inhibitors. A 48 h treatment resulted in diminished cell viability. Calculated IC50 values (halfmaximal inhibitory concentrations) were 25 µM, 15 µM and 30 µM for CarbZDNaph, CarbZDChin
and Rev-5901, respectively. The detailed analysis of mechanism revealed an induction of caspasedependent apoptosis and autophagy. In the presence of chloroquine, an autophagy inhibitor, we
observed an increased mortality of cells, implying a cytoprotective role of autophagy. Our in vivo
experiment reports tumor growth attenuation in animals treated with CarbZDChin. Compounds
CarbZDNaph and Rev-5901 lacked an in vivo efficacy. The results presented in this study display a
strong effect of compound CarbZDChin on malignant cell growth. Having in mind the important
role of inflammation in cancer development, these results have a significant impact and are worthy of
further evaluation.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87763 |
| Date | 27 October 2023 |
| Creators | Paskas, Svetlana, Murganic, Blagoje, Kuhnert, Robert, Hey-Hawkins, Evamarie, Mijatovic, Sanja, Maksimovic-Ivanic, Danijela |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 4503 |
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