1,2,3,6-Tetra-O-Galloyl-β-D-Glucopyranose Induces Apoptosis and Ferroptosis in Colon Cancer Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway
Related Experiment Video
Updated: Sep 13, 2025

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Suhyeon Kim1, MinKyun Na2, Sangtaek Oh1
1Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.
Abstract:
Molecular irregularities in the canonical Wnt pathway that lead to the stabilization of β-catenin are common in colon cancer. Here, we identified 1,2,3,6-Tetra-O-galloyl-β-D-glucopyranose (TAGP), separated from Trapa japonica, as an inhibitor of canonical Wnt signaling. TAGP facilitated the phosphorylation of Ser33/37 and the degradation of β-catenin, which had accumulated due to Wnt3a-conditioned medium or the inhibitor 6-bromoindirubin-3'-oxime that targets glycogen synthase kinase-3β (GSK-3β). Additionally, TAGP lowered the levels of Cyclin D1 and c-Myc, which are regulated by β-catenin/T-cell factor (TCF) and showed antiproliferative activity in colon cancer cells. Furthermore, TAGP triggered apoptosis, as demonstrated by the activation of caspases 3 and 7, in conjunction with raising the number of Annexin-V-positive cells. It also promoted ferroptosis, as shown by the buildup of lipid peroxides and Fe2+ in the cells. Taken together, TAGP enhances β-catenin turnover, indicating its potential as a chemotherapeutics for colon cancer in humans.
Insights
1,2,3,6-Tetra-O-galloyl-β-D-glucopyranose (TAGP) from Trapa japonica inhibits colon cancer growth by promoting β-catenin degradation. TAGP also induces apoptosis and ferroptosis, showing potential as a novel colon cancer therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Canonical Wnt pathway signaling is frequently dysregulated in colon cancer, leading to β-catenin stabilization.
- Targeting molecular aberrations in this pathway presents a therapeutic opportunity for colon cancer treatment.
Purpose of the Study:
- To identify novel inhibitors of the canonical Wnt signaling pathway.
- To investigate the anti-cancer effects of 1,2,3,6-Tetra-O-galloyl-β-D-glucopyranose (TAGP) in colon cancer cells.
Main Methods:
- TAGP was isolated from Trapa japonica.
- Effects of TAGP on β-catenin phosphorylation and degradation were assessed.
- Cell proliferation, apoptosis, and ferroptosis markers were analyzed in colon cancer cells treated with TAGP.
Main Results:
- TAGP inhibited canonical Wnt signaling by promoting β-catenin phosphorylation and subsequent degradation.
- TAGP reduced levels of Wnt/β-catenin target genes, Cyclin D1 and c-Myc.
- TAGP exhibited antiproliferative activity, induced apoptosis (caspase activation, Annexin-V positivity), and promoted ferroptosis (lipid peroxidation, Fe2+ accumulation) in colon cancer cells.
Conclusions:
- TAGP enhances β-catenin turnover, thereby inhibiting colon cancer cell proliferation.
- TAGP induces both apoptosis and ferroptosis, suggesting a multi-targeted therapeutic mechanism.
- TAGP demonstrates significant potential as a chemotherapeutic agent for human colon cancer.
More Related Videos
09:18Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
06:07Evaluating Cell Death Using Cell-Free Supernatant of Probiotics in Three-Dimensional Spheroid Cultures of Colorectal Cancer Cells
Published on: June 13, 2020
Related Concept Videos
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Apoptosis
Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
The Intrinsic Apoptotic Pathway
Canonical Wnt Signaling Pathway