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Lentinan inhibits melanoma development by regulating the AKT/Nur77/Bcl-2 signaling axis

Summary

This research demonstrates that lentinan, a compound from shiitake mushrooms, can effectively inhibit melanoma (a dangerous skin cancer) in laboratory studies. The compound works by triggering cancer cells to self-destruct through a specific cellular pathway involving three key proteins: AKT, Nur77, and Bcl-2. Importantly, the treatment showed no significant toxic side effects in animal models, suggesting it could be developed as a new cancer therapy option.

Background

Melanoma is a highly malignant and difficult-to-treat skin cancer with poor prognosis in advanced stages due to resistance to conventional treatments. Lentinan (LNT), extracted from Lentinus edodes (shiitake mushroom), is a β-(1,3)-glucan polysaccharide with demonstrated anti-tumor properties. This study explores LNT’s potential as a new therapeutic approach for melanoma treatment.

Objective

To establish a new approach for melanoma treatment by analyzing the pharmacological properties of lentinan and determining whether LNT regulates the Nur77/Bcl-2 apoptotic pathway to inhibit melanoma growth.

Results

LNT significantly inhibited melanoma growth and proliferation in vivo and in vitro by decreasing PARP1 and PCNA expression while decreasing Nur77 and increasing Bcl-2 expression. LNT promoted Nur77 translocation from nucleus to cytoplasm and increased co-localization with mitochondrial protein Bcl-2, inducing apoptosis. AKT phosphorylation inhibition played a key role in mediating the Nur77/Bcl-2 pathway activation.

Conclusion

LNT inhibits melanoma tumor growth and promotes apoptosis by regulating the AKT/Nur77/Bcl-2 signaling pathway. These findings highlight LNT’s potential for drug development and clinical treatment of melanoma, with no significant toxic effects observed.
  • Published in:Journal of Cancer,
  • Study Type:Experimental Study,
  • Source: PMID: 39744474, DOI: 10.7150/jca.100863
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