Description:
Lipoxygenases convert polyunsaturated fatty acids into biologically active metabolitessuch as inflammatory mediators—prostaglandins and leukotrienes. The inhibition of lipoxygenasesis increasingly employed in the treatment of cancer. We evaluated the anticancer potential of twonovel 5-lipoxygenase inhibitors, named CarbZDNaph and CarbZDChin, which are analogues ofthe commercially available inhibitor Rev-5901. The in vitro segment of this study was conductedon a mouse colorectal carcinoma cell line—CT26CL25. For an in vivo model, we induced tumorsin BALB/c mice by the implantation of CT26CL25 cells, and we treated the animals with potentialinhibitors. 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, CarbZDChinand Rev-5901, respectively. The detailed analysis of mechanism revealed an induction of caspasedependent apoptosis and autophagy. In the presence of chloroquine, an autophagy inhibitor, weobserved an increased mortality of cells, implying a cytoprotective role of autophagy. Our in vivoexperiment reports tumor growth attenuation in animals treated with CarbZDChin. CompoundsCarbZDNaph and Rev-5901 lacked an in vivo efficacy. The results presented in this study display astrong effect of compound CarbZDChin on malignant cell growth. Having in mind the importantrole of inflammation in cancer development, these results have a significant impact and are worthy offurther evaluation.