Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

References

    1. Arung E, Yoshikawa K, Shimizu K, Kondo R (2010) Isoprenoid-substituted flavonoids from wood of Artocarpus heterophyllus on B16 melanoma cells: cytotoxicity and structural criteria. Fitoterapia 81(2):120–123. https://doi.org/10.1016/j.fitote.2009.08.001 - DOI - PubMed
    1. Bahrami Y, Bouk S, Kakaei E, Taheri M (2022) Natural products from actinobacteria as a potential source of new therapies against colorectal cancer: a review. Front Pharmacol 13:929161. https://doi.org/10.3389/fphar.2022.929161 - DOI - PubMed - PMC
    1. Bordonaro M (2013) Crosstalk between Wnt signaling and RNA processing in colorectal cancer. J Cancer 4(2):96–103. https://doi.org/10.7150/jca.5470 - DOI - PubMed - PMC
    1. Bray F, Jemal A, Grey N, Ferlay J, Forman D (2012) Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 13(8):790–801. https://doi.org/10.1016/s1470-2045(12)70211-5 - DOI - PubMed
    1. Brigelius-Flohe R, Flohe L (2020) Regulatory phenomena in the glutathione peroxidase superfamily. Antioxid Redox Signal 33(7):498–516. https://doi.org/10.1089/ars.2019.7905 - DOI - PubMed

Publication types

LinkOut - more resources