Pentagalloylglucose Suppresses Glioblastoma Progression via Wnt/β-Catenin Pathway Inhibition and EMT Reversal

Ebrahimi Hosseini, Seyedeh Saba

doi:10.22034/ppmj.2026.735673

Pentagalloylglucose Suppresses Glioblastoma Progression via Wnt/β-Catenin Pathway Inhibition and EMT Reversal

Document Type : Original Article

Author

Seyedeh Saba Ebrahimi Hosseini ^¶

Biotechnology Research Center, Bushehr Branch, Persian Gulf University, Bushehr, Iran.

https://doi.org/10.22034/ppmj.2026.735673

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.

Keywords

Glioblastoma, Pentagalloylglucose, Epithelial-Mesenchymal Transition, Wnt/&beta

-catenin signaling

1. Rusak A, Wiatrak B, Krawczyńska K, Górnicki T, Zagórski K, Zadka Ł, et al. Starting points for the development of new targeted therapies for glioblastoma multiforme. Translational Oncology. 2025;51:102187.
2. Banu Z. Glioblastoma multiforme: a review of its pathogenesis and treatment. Int Res J Pharm. 2019;9:7-12.
3. Iwadate Y. Epithelial‑mesenchymal transition in glioblastoma progression. Oncology letters. 2016;11(3):1615-20.
4. Pala A, Karpel-Massler G. Epithelial to Mesenchymal Transition and Progression of. Clinical Management and Evolving Novel Therapeutic Strategies For Patients With Brain Tumors. 2013:277.
5. Barzegar Behrooz A, Talaie Z, Jusheghani F, Łos MJ, Klonisch T, Ghavami S. Wnt and PI3K/Akt/mTOR survival pathways as therapeutic targets in glioblastoma. International journal of molecular sciences. 2022;23(3):1353.
6. He L, Zhou H, Zeng Z, Yao H, Jiang W, Qu H. Wnt/β‐catenin signaling cascade: A promising target for glioma therapy. Journal of cellular physiology. 2019;234(3):2217-28.
7. Lee Y, Lee J-K, Ahn SH, Lee J, Nam D-H. WNT signaling in glioblastoma and therapeutic opportunities. Laboratory investigation. 2016;96(2):137-50.
8. Wen C, Dechsupa N, Yu Z, Zhang X, Liang S, Lei X, et al. Pentagalloyl glucose: a review of anticancer properties, molecular targets, mechanisms of action, pharmacokinetics, and safety profile. Molecules. 2023;28(12):4856.
9. Fan C-W, Tang J, Jiang J-C, Zhou M-M, Li M-S, Wang H-S. Pentagalloylglucose suppresses the growth and migration of human nasopharyngeal cancer cells via the GSK3β/β-catenin pathway in vitro and in vivo. Phytomedicine. 2022;102:154192.
10.Amawi H, Ashby Jr CR, Samuel T, Peraman R, Tiwari AK. Polyphenolic nutrients in cancer chemoprevention and metastasis: Role of the epithelial-to-mesenchymal (EMT) pathway. Nutrients. 2017;9(8):911.
11.Iser IC, Pereira MB, Lenz G, Wink MR. The epithelial‐to‐mesenchymal transition‐like process in glioblastoma: an updated systematic review and in silico investigation. Medicinal Research Reviews. 2017;37(2):271-313.
12.Tian Y, Li J, Cai X, Huang Y, Wang X, Liu Q, et al. Molecular drivers of epithelial-mesenchymal transition (EMT) in glioblastoma and impact on therapy resistance. Pathology-Research and Practice. 2025;272:156111.
13.Kantapan J, Innuan P, Kongkarnka S, Sangthong P, Dechsupa N. Pentagalloyl Glucose from Bouea macrophylla Suppresses the Epithelial–Mesenchymal Transition and Synergizes the Doxorubicin-Induced Anticancer and Anti-Migration Effects in Triple-Negative Breast Cancer. Pharmaceuticals. 2024;17(12):1729.
14.Yang H, Yue GG-L, Leung P-C, Wong C-K, Zhang Y-J, Bik-San Lau C. Anti-metastatic effects of 1, 2, 3, 4, 6-Penta-O-galloyl-β-D-glucose in colorectal cancer: Regulation of cathepsin B-mediated extracellular matrix dynamics and epithelial-to-mesenchymal transition. Pharmacological Research. 2022;184:106457.
15.Kim E-Y, Lee S-U, Kim YH. 1, 2, 3, 4, 6-Penta-O-galloyl-β-D-glucose Inhibits CD44v3, a cancer stem cell marker, by regulating its transcription factor, in human pancreatic cancer cell line. Animal Cells and Systems. 2022;26(6):328-37.
16.Zhao W, Wang Y, Hao W, Zhao M, Peng S. In vitro inhibition of fatty acid synthase by 1, 2, 3, 4, 6-penta-O-galloyl-β-d-glucose plays a vital role in anti-tumour activity. Biochemical and Biophysical Research Communications. 2014;445(2):346-51.