Cyclocarya paliurus Polysaccharide Inhibits Glioma Cell U251 Proliferation, Migration, and Invasion and Promotes Apoptosis via the GSK3β/β-Catenin Signaling Pathway

Abstract

Objective. To investigate the effects of Cyclocarya paliurus polysaccharide (CPP) on the proliferation, migration, invasion, and apoptosis of human glioma U251 cells and further explore the underlying mechanism. Methods. U251 cells were cultured in vitro and treated with various concentrations (25, 50, 75, 100, 125, and 150 μmol/L) of CPP for 24, 48, and 72 h. Cell counting kit-8 was used to detect the activity of cell proliferation. Wound-healing assay, Transwell assay, and flow cytometry were used to measure the effects of CPP on the migration, invasion, and apoptosis of U251 cells, respectively. Western blotting was used to determine the protein expression involved in the GSK3β/β-catenin signaling pathway and its downstream genes related to proliferation, migration, invasion, and apoptosis including Cyr61, CCND1, Vimentin, and Slug. Meanwhile, qRT-PCR was used to detect the mRNA levels of Cyr61, CCND1, Vimentin, and Slug. Results. We found that CPP not only could inhibit the proliferation, migration, and invasion of U251 cells but also promote its apoptosis in vitro. Besides, CPP could significantly inhibit the phosphorylation and decrease the protein levels of GSK3 β at ser9 site (p<0.05), and thus increasing the phosphorylation of β-Catenin at ser33/37 site (p<0.05), resulting in β-Catenin degradation. In addition, we also found that CPP could downregulate the mRNA (p<0.05) and protein expression (p<0.05) of downstream genes of GSK3 β/β-catenin signaling pathway including Cyr61, CCND1, Vimentin, and Slug, which are related to proliferation, migration, invasion, and apoptosis. Conclusion. CPP could inhibit the expression of GSK3β, promote the degradation of β-catenin, and downregulate the levels of GSK3β/β-catenin downstream genes including Cyr61, CCND1, Vimentin, and Slug, which regulate the proliferation, migration, invasion, and apoptosis of glioma cells.

Bioactive polysaccharides and small molecules from the native North American fungus Echinodontium tinctorium

“…arrest in U87MG glioblastoma cells (Arcella et al, 2017). Cytotoxic triterpenoids from Antrodia camphorata (Li et al, 2020), polysaccharides from medicinal plants like Angelica sinensis (APs) (Zhand et al, 2017), Cyclocarya paliurus (CPP) (Du et al, 2020) and Aconitum coreanum (ACP1) (Sun et al, 2018) have also shown to induce apoptosis in U87MG and U251 glioblastoma cell lines. 106…”