Damnacanthal Suppresses TCF4 Expression in Colorectal Cancer Cells

Despite advances in cancer therapy, the incidence and death rates of patients with colorectal cancer are still high, underscoring the need for new treatment strategies. Damnacanthal, an anthraquinone found in Morinda citrifolia L. (common name noni), is known to induce apoptosis and inhibit cell growth in various types of cancer cells. This study aimed to elucidate the anticancer mechanism of damnacanthal in colorectal cancer.

Damnacanthal was tested on colorectal cancer cell lines (HCT116 and SW480) as well as colorectal cancer spheroids. We evaluated β-catenin activity by TOP/FOPFlash assay. Western blotting and quantitative polymerase chain reaction were used to measure β-catenin and T-cell factor 4 (TCF4) expression.

We found that damnacanthal reduced the transcriptional activity of β-catenin, resulting in the down-regulation of its target genes. Additionally, damnacanthal reduced the expression of TCF4, a key protein in the WNT/β-catenin pathway, in a dose-dependent manner. We also observed a decrease in DNA-bound TCF4 when colorectal cancer cells were treated with damnacanthal.

Damnacanthal exerts anticancer activity by reducing TCF4 expression in colorectal cancer cells. Our data provide novel insights into the molecular mechanism of damnacanthal in colorectal cancer cells, offering a promising new treatment strategy.