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Lentinan inhibits colorectal cancer stemness by binding CD133 and suppressing the CD133/p85/p-AKT signaling axis

Summary

Researchers discovered that lentinan, a natural compound from shiitake mushrooms, can specifically target and kill cancer stem cells in colorectal cancer by binding to a protein called CD133. This is significant because cancer stem cells are the reason why cancers come back even after treatment. By blocking a specific pathway these cells use to survive, lentinan may help prevent cancer recurrence and reduce the side effects associated with traditional chemotherapy.

Background

Colorectal cancer (CRC) is the third most common cancer globally with high recurrence and metastasis rates driven by cancer stem cells (CSCs). Current chemotherapy fails to eliminate CSCs, leading to drug resistance and tumor recurrence. Lentinan, a β-glucan from Lentinus edodes, has demonstrated immune-enhancing and antitumor properties, but its potential against CRC stemness remains unexplored.

Objective

This study investigates whether lentinan (SLNT) can suppress CRC stemness through CD133 targeting and to elucidate the underlying molecular mechanisms involved in this process.

Results

SLNT significantly suppressed CRC proliferation and stemness in both cell lines and xenograft models. Direct binding between SLNT and CD133 was confirmed (KD=1.59×10⁻⁷M) with stronger affinity than to immune receptors. SLNT inhibited CD133 expression and suppressed the CD133/p85/p-AKT signaling axis, with CD133⁺ cells showing greater sensitivity to SLNT treatment.

Conclusion

Lentinan directly binds to CD133 and inhibits CRC stemness through suppression of the CD133/p85/p-AKT signaling pathway. These findings demonstrate the anti-CSC potential of natural polysaccharides and suggest lentinan as a promising therapeutic option for colorectal cancer with reduced drug resistance and recurrence risk.
  • Published in:Frontiers in Pharmacology,
  • Study Type:In vitro and In vivo Experimental Study,
  • Source: 10.3389/fphar.2025.1725716
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