Personalized and Precision Medicine Journal

Abstract Background: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor. GBM exhibits rapid growth and invasiveness along with a nadir prognosis. Epithelial–mesenchymal transition (EMT), combined with activated Wnt/β-catenin signaling, contributes to GBM progression and associated therapy resistance. Pentagalloylglucose (PGG), a polyphenolic compound from nature, has been shown to be anticancer in multiple cancers by inhibiting proliferation, migration, and EMT. The objectives are to demonstrate the effects of PGG on GBM cells and examine the modulation of EMT and the Wnt/β-catenin pathway.
Methods: U87-MG cells were treated with PGG (0.5–40 µM) for 24, 48, and 72 hours. Cell viability was assessed using the MTT assay. The expression levels of epithelial–mesenchymal transition (EMT) markers, including E-cadherin, N-cadherin, Vimentin, Snail, Slug, as well as β-catenin, were quantified by qRT-PCR. Cell migration was evaluated using a wound healing assay. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test.
Results: PGG demonstrated a marked reduction in cell viability in a dose- and duration-dependent manner with IC₅₀ values at 18.4, 12.7, and 8.9 µM at 24, 48, and 72 hours, respectively. The upregulation of E-cadherin and downregulation of N-cadherin, Vimentin, and the Snail protein show that mesenchymal markers are being transcriptionally silenced. It was also a striking loss of β-catenin expression, which suggests Wnt/β-catenin suppression. Wound healing assay showed that PGG treatment resulted in a marked reduction of cell migration.
Conclusion: PGG significantly inhibits the progression of GBM by inhibiting EMT and downregulating the Wnt/β-catenin signaling pathways. Overall, PGG has potential as a natural, low-toxicity therapeutic or combinatory drug for glioblastoma, and future studies in vivo and in human trials will be needed to reaffirm this conclusion.