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Damnacanthal Suppresses TCF4 Expression in Colorectal Cancer Cells
Jaehak Lee1, Hayeun Kim1, Jiyoung Moon1
1Laboratory of Signal Transduction, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea.
Anticancer Research
|June 27, 2025
Summary
Damnacanthal, derived from noni, shows anticancer effects in colorectal cancer by inhibiting the WNT/β-catenin pathway and reducing T-cell factor 4 (TCF4) expression.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Colorectal cancer (CRC) remains a significant health concern with high mortality rates.
- Existing therapies have limitations, necessitating novel treatment strategies.
- Damnacanthal, an anthraquinone from *Morinda citrifolia* (noni), exhibits known anticancer properties.
Purpose of the Study:
- To investigate the anticancer mechanism of damnacanthal in colorectal cancer.
- To elucidate how damnacanthal affects key signaling pathways in CRC cells.
Main Methods:
- Damnacanthal was tested on colorectal cancer cell lines (HCT116, SW480) and spheroids.
- Beta-catenin activity was assessed using the TOP/FOPFlash assay.
- Western blotting and qPCR measured beta-catenin and T-cell factor 4 (TCF4) expression.
Main Results:
- Damnacanthal reduced beta-catenin transcriptional activity and its target gene expression.
- Damnacanthal dose-dependently decreased TCF4 protein expression.
- Treatment with damnacanthal led to reduced DNA-bound TCF4 in colorectal cancer cells.
Conclusions:
- Damnacanthal demonstrates anticancer activity in colorectal cancer by down-regulating TCF4 expression.
- This study reveals a novel molecular mechanism for damnacanthal's action in CRC.
- Damnacanthal presents a promising therapeutic candidate for colorectal cancer treatment.
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