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A Novel Erinacine S Derivative from Hericium erinaceus Overcomes Chemoresistance in Colorectal Cancer Cells by Enhancing TRAIL/TNFR1/DR5 Expression through Histone Acetylation

Summary

Researchers found that erinacine S, a compound from Lion’s Mane mushroom, can help kill colorectal cancer cells that have become resistant to chemotherapy drugs. The compound works by activating death pathways in cancer cells and modifying how genes are expressed. In mouse studies, erinacine S significantly reduced tumor growth compared to standard chemotherapy alone. This suggests Lion’s Mane mushroom derivatives could potentially be developed as a natural treatment option for patients with drug-resistant colorectal cancer.

Background

Hericium erinaceus, known as Lion’s Mane mushroom, contains bioactive diterpenoid derivatives including erinacine S. Colorectal cancer (CRC) is a prevalent cancer characterized by cancer stem cells that contribute to chemoresistance and sustained tumor growth. Previous studies have explored H. erinaceus extracts, but the specific mechanisms of erinacine S from mycelium in chemoresistant CRC remain unclear.

Objective

This study aims to investigate the molecular mechanisms by which erinacine S, derived from H. erinaceus mycelium, inhibits chemoresistant human colorectal cancer cells. The research seeks to elucidate how erinacine S enhances apoptosis through TRAIL/TNFR1/DR5 expression and histone acetylation modifications.

Results

Erinacine S treatment significantly induced apoptosis and suppressed aggressiveness of chemoresistant HCT-116/FUR cells, with remarkable inhibitory effects on tumor growth in xenograft models. Treatment upregulated TRAIL, TNFR1, and DR5 expression while downregulating p-AKT, p-ERK, HIF1α, PCNA, and NFκB. The PAK/FAK/p300 pathway activation triggered histone H3K9K14ac modifications at TRAIL, TNFR1, and DR5 promoters.

Conclusion

Erinacine S demonstrates significant anti-cancer effects in both in vitro and in vivo models through inhibition of invasion, migration, and proliferation. The compound operates via epigenetic histone acetylation and inactivation of the CXCR4/PI3K/Akt/HIF-1 pathway, showing promise as a natural agent for clinical therapy of chemoresistant CRC.
  • Published in:International Journal of Medical Sciences,
  • Study Type:In vitro and In vivo Experimental Study,
  • Source: PMID: 41209562, DOI: 10.7150/ijms.119894
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