# In Vitro Inhibition of Colon Cancer Stem Cells by Natural Polysaccharides Obtained from Wheat Cell Culture

## TL;DR

This study shows that natural polysaccharides from wheat can inhibit colon cancer stem cells, potentially reducing tumor recurrence.

## Contribution

The novel finding is that wheat polysaccharides inhibit cancer stem cells and promote their differentiation, not just apoptosis.

## Key findings

- Wheat polysaccharides inhibit both differentiated and stem-like colon cancer cells.
- Fractions rich in xylose and galacturonic acid show strong anti-cancer stem cell activity.
- Polysaccharides reduce β-catenin and c-Myc, and increase caspase-3, suggesting a differentiation-promoting mechanism.

## Abstract

Natural polysaccharides (PSs) have shown inhibitory effects on differentiated cancer cells (DCCs), but their activity against cancer stem cells (CSCs) remains poorly understood. Here, we report that PSs from wheat cell cultures (WCCPSs) inhibit the proliferation of both DCCs and CSCs derived from HCT-116 colorectal cancer cells. Among them, NA and DC fractions showed the strongest anti-CSC activity. NA, rich in xylose, was effective at lower concentrations, while DC, enriched in xylose and galacturonic acid (GalUA), exhibited higher potency, with a lower IC50 and preferential activity against CSCs at higher doses. WCCPSs reduced β-catenin levels, and some fractions also downregulated Ep-CAM, CD44, and c-Myc. Notably, DC increased caspase-3 without inducing cytochrome C and caspase-8 overexpression, suggesting a mechanism promoting CSC differentiation rather than apoptosis. Correlation analysis linked xylose content to reduced c-Myc expression, and GalUA levels to increased caspase-3. These results suggest that WCCPS bioactivity may be related to their monosaccharide composition. Overall, our findings support the potential of wheat-derived PSs as CSC-targeting agents that suppress self-renewal and promote differentiation, offering a promising approach to reduce tumor aggressiveness and recurrence.