Sanggenon C inhibits glioblastoma cell migration and invasion by promoting ubiquitination of β-catenin

Abstract:

Glioblastoma is a malignant and highly invasive tumor, which requires new approaches to search for chemotherapeutic agents. Sanggenon C (SC) mainly exists in the root bark of white mulberry. Although its anti-tumor effects have been reported in some cancers, the mechanism remains unclear. In this study, we used microscopic observation, transwell assay, and immunofluorescence assay to verify the effect of Sanggenon C on the migration and invasion of glioblastoma cells. We then carried out the gene set enrichment analysis (GESA), real-time qPCR assay and ubiquitination assay to delineate the molecule mechanism by which Sanggenon C affects the migration and invasion ability of glioblastoma. With the addition of Sanggenon C, glioblastoma cells were rounded up, with the migration and invasion ability weakened as verified by transwell assay and immunofluorescence assay. The results of GESA suggested that SC might regulate the expression of genes associated with migration and invasion and affect the activity of Wnt/β-catenin signaling pathway. Western blotting revealed that Sanggenon C promoted the ubiquitination of β-catenin to reduce the levels of β-catenin and its downstream proteins. This was further supported by the results of real-time qPCR analysis of target genes of β-catenin. Taken together, SC inhibits glioblastoma cell migration and invasion by enhancing β-catenin ubiquitination. Our work suggests a new direction for the treatment of glioblastoma.

Key words:glioblastoma;Sanggenon C;migration;invasion;the ubiquitination of β-catenin