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Article Publish Status: FREE
Abstract Title:

Urolithin A Inhibits Epithelial-Mesenchymal Transition in Lung Cancer Cells via P53-Mdm2-Snail Pathway.

Abstract Source:

Onco Targets Ther. 2021 ;14:3199-3208. Epub 2021 May 17. PMID: 34040386

Abstract Author(s):

Feng Cheng, Jintao Dou, Yong Zhang, Xiang Wang, Huijun Wei, Zhijian Zhang, Yuxiang Cao, Zhihao Wu

Article Affiliation:

Feng Cheng

Abstract:

Purpose: The epithelial-to-mesenchymal transition (EMT) is a fundamental process in tumor progression that endows cancer cells with migratory and invasive potential. Snail, a zinc finger transcriptional repressor, plays an important role in the induction of EMT by directly repressing the key epithelial marker E-cadherin. Here, we assessed the effect of urolithin A, a major metabolite from pomegranate ellagitannins, on Snail expression and EMT process.

Methods: The role of Snail in urolithin A-induced EMT inhibition in lung cancer cells was explored by wound healing assay and cell invasion assay. The qRT-PCR and CHX assay were performed to investigate how urolithin A regulates Snail expression. Immunoprecipitation assays were established to determine the effects of urolithin A in mdm2-Snail interaction. In addition, the expression of p53 was manipulated to explore its effect on the expression of mdm2 and Snail.

Results: The urolithin A dose-dependently upregulated epithelial marker and decreased mesenchymal markers in lung cancer cells. In addition, exposure to urolithin A decreased cell migratory and invasive capacity. We have further demonstrated that urolithin A inhibits lung cancer cell EMT by decreasing Snail protein expression and activity. Mechanistically, urolithin A disrupts the interaction of p53 and mdm2 which leads Snail ubiquitination and degradation.

Conclusion: We conclude that urolithin A could inhibit EMT process by controlling mainly Snail expression. These results highlighted the role of pomegranate in regulation of EMT program in lung cancer.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Anti-metastatic : CK(1972) : AC(1481)

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