1,2,3,6-Tetra-O-Galloyl-β-D-Glucopyranose Induces Apoptosis and Ferroptosis in Colon Cancer Cells by Inhibiting the

Suhyeon Kim1, MinKyun Na2, Sangtaek Oh1

  • 1Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 02707, Republic of Korea.

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.

Related Concept Videos

Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
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...
7.8K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
12.0K
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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...
4.8K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
4.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.9K
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.9K