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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

The Natural Flavonoid Naringenin Inhibits the Cell Growth of Wilms Tumor in Children by Suppressing TLR4/NF-κB Signaling

Author(s): Hongtao Li*, Peng Chen, Lei Chen and Xinning Wang

Volume 21, Issue 9, 2021

Published on: 18 August, 2020

Page: [1120 - 1126] Pages: 7

DOI: 10.2174/1871520620999200818155814

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Abstract

Background: Nuclear Factor-kappa B (NF-κB) is usually activated in Wilms Tumor (WT) cells and plays a critical role in WT development.

Objective: The study's purpose was to screen for a NF-κB inhibitor from the natural product library and explore its effects on WT development.

Methods: Luciferase assay was employed to assess the effects of natural chemicals on NF-κB activity. CCK-8 assay was conducted to assess cell growth in response to naringenin. WT xenograft model was established to analyze the effect of naringenin in vivo. Quantitative real-time PCR and Western blot were performed to examine the mRNA and protein levels of relative genes, respectively.

Results: Naringenin displayed a significant inhibitory effect on NF-κB activation in SK-NEP-1 cells. In SKNEP- 1 and G-401 cells, naringenin inhibited p65 phosphorylation. Moreover, naringenin suppressed TNF-α- induced p65 phosphorylation in WT cells. Naringenin inhibited TLR4 expression at both mRNA and protein levels in WT cells. CCK-8 staining showed that naringenin inhibited cell growth of the two above WT cells in doseand time-dependent manner, whereas Toll-Like Receptor 4 (TLR4) overexpression partially reversed the above phenomena. Besides, naringenin suppressed WT tumor growth in a dose- and time-dependent manner in vivo. Western blot found that naringenin inhibited TLR4 expression and p65 phosphorylation in WT xenograft tumors.

Conclusion: Naringenin inhibits WT development via suppressing TLR4/NF-κB signaling.

Keywords: Naringenin, wilms tumor, TLR4, NF-κB, flavonoids, luciferase assay.

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