El-Fadeal, Noha M. Abd published the artcileAntitumor activity of nitazoxanide against colon cancers: molecular docking and experimental studies based on Wnt/beta-catenin signaling inhibition, Quality Control of 55981-09-4, the main research area is antitumor activity nitazoxanide colon cancer mol docking signaling inhibition; PCNA; Wnt/β-catenin signaling; apoptosis; molecular docking; mouse colon cancer; nitazoxanide.
In colon cancer, wingless (Wnt)/ β-catenin signaling is frequently upregulated; however, the creation of a mol. therapeutic agent targeting this pathway is still under investigation. This research aimed to study how nitazoxanide can affect Wnt/ β-catenin signaling in colon cancer cells (HCT-116) and a mouse colon cancer model. Our study included 2 experiments; the first was to test the cytotoxic activity of nitazoxanide in an in vitro study on a colon cancer cell line (HCT-116) vs. normal colon cells (FHC) and to highlight the proapoptotic effect by MTT assay, flow cytometry and real-time polymerase chain reaction (RT-PCR). The second experiment tested the in vivo cytotoxic effect of nitazoxanide against 1,2-dimethylhydrazine (DMH) prompted cancer in mice. Mice were grouped as saline, DMH control and DMH + nitazoxanide [100 or 200 mg per kg]. Colon levels of Wnt and β-catenin proteins were assessed by Western blotting while proliferation was measured via immunostaining for proliferating cell nuclear antigen (PCNA). Treating HCT-116 cells with nitazoxanide (inhibitory concentration 50 (IC50) = 11.07 μM) revealed that it has a more cytotoxic effect when compared to 5-flurouracil (IC50 = 11.36 μM). Moreover, it showed relatively high IC50 value (non-cytotoxic) against the normal colon cells. Nitazoxanide induced apoptosis by 15.86-fold compared to control and arrested the cell cycle. Furthermore, nitazoxanide upregulated proapoptotic proteins (P53 and BAX) and caspases but downregulated BCL-2. Nitazoxanide downregulated Wnt/ β-catenin/glycogen synthase kinase-3β (GSK-3β) signaling and PCNA staining in the current mouse model. Hence, our findings highlighted the cytotoxic effect of nitazoxanide and pointed out the effect on Wnt/ β-catenin/GSK-3β signaling.
International Journal of Molecular Sciences published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Quality Control of 55981-09-4.
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