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. 2024 Feb;397(2):1115-1125.
doi: 10.1007/s00210-023-02668-2. Epub 2023 Aug 23.

GPX2 acts as an oncogene and cudraflavone C has an anti-tumor effect by suppressing GPX2-dependent Wnt/β-catenin pathway in colorectal cancer cells

Zhuo Wu  1 , Su Zhou  2 , Dan Liang  3 , Lan Mu  4
Affiliations

GPX2 acts as an oncogene and cudraflavone C has an anti-tumor effect by suppressing GPX2-dependent Wnt/β-catenin pathway in colorectal cancer cells

Zhuo Wu et al. Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb.

Abstract

Colorectal carcinoma (CRC) is a common cancer associated with poor prognosis, and cudraflavone C (Cud C) is a natural flavonol with reported anti-CRC capacity. However, the precise mechanisms underlying the anti-CRC effect require further demonstration. The aim of present study was to evaluate the impact of Cud C on the cell viability and apoptosis of CRC cells and to determine the underlying mechanisms. The Human Protein Atlas (THPA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyze the expression status of glutathione peroxidase 2 (GPX2) in CRC. Cell viability was examined using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to evaluate apoptosis. The levels of gene transcription and protein expression of GPX2, caspase-3, cleaved caspase-3), β-catenin, and c-Myc were determined by RT-qPCR and Western blotting. Our results showed that GPX2 was overexpressed in CRC as compared to normal tissue and the extent of GPX2 overexpression is greatest in CRC when compared with other cancers according to GEPIA and THPA databases. GPX2 knockdown significantly suppressed the cell viability, induced apoptosis of CRC cell lines, and restrained the activity of Wnt/β-catenin pathway. Cud C treatment decreased cell viability, induced apoptosis in CRC cell lines, and diminished the expression level of GPX2-dependent activation of Wnt/β-catenin pathway, while such effects can be abolished by GPX2 overexpression. In conclusion, Cud C suppressed GPX2-dependent Wnt/β-catenin pathway to exert anti-CRC function.

Keywords: Apoptosis; Colorectal carcinoma; Cudraflavone C; GPX2; Viability; Wnt/β-catenin pathway.

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