Carborane-Based Analog of Rev-5901 Attenuates Growth of Colon Carcinoma In Vivo.
2022
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Аутори:
Paskaš, SvetlanaMurganić, Blagoje
Kuhnert, Robert
Hey-Hawkins, Evamarie
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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 (half-maximal 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 caspase-dependent 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.
Кључне речи:
5-lipoxygenase; CT26CL25; Rev-5901; Carboranes; Colorectal carcinomaИзвор:
Molecules (Basel, Switzerland), 2022, 27, 14, 4503-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
DOI: 10.3390/molecules27144503
ISSN: 1420-3049
PubMed: 35889376
WoS: 000832129900001
Scopus: 2-s2.0-85135623350
URI
https://www.mdpi.com/1420-3049/27/14/4503http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9321230
http://radar.ibiss.bg.ac.rs/handle/123456789/5088