Apoptosis Induced by 9,11-Dehydroergosterol Peroxide from Ganoderma Lucidum Mycelium in Human Malignant Melanoma Cells is Mcl-1 Dependent

Author: mycolabadmin
2018-05-17
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Summary

This research investigated how a natural compound found in the medicinal mushroom Ganoderma lucidum can kill melanoma cancer cells. The compound works by targeting a specific protein that helps cancer cells survive, ultimately causing the cancer cells to self-destruct while leaving healthy cells unharmed. Impact on everyday life: – Provides a potential new treatment option for aggressive skin cancer – Demonstrates the medical value of traditional medicinal mushrooms – Shows how natural compounds can be developed into targeted cancer therapies – Offers hope for patients with treatment-resistant melanoma – Supports the importance of preserving and studying natural resources for medicine

Background

Melanoma is one of the most aggressive forms of skin cancer, representing less than 5% of cases but causing the majority of skin cancer deaths. This is largely due to melanoma cells’ resistance to conventional chemotherapy and biological treatments. Defects in apoptotic signaling in melanoma cells contribute to unchecked proliferation and immortalization. 9,11-dehydroergosterol peroxide (9(11)-DHEP) is a fungal secondary metabolite found in mushrooms that has shown cytotoxic effects on various cancer cells, though its mechanism of action is not fully understood.

Objective

To investigate the antitumor mechanisms of 9(11)-DHEP purified from Ganoderma lucidum mycelium on A375 human malignant melanoma cells and elucidate its molecular pathways for inducing cancer cell death.

Results

9(11)-DHEP showed selective toxicity toward cancer cells, with A375 melanoma cells being most sensitive (IC50 = 9.147 μg/ml). The compound induced apoptosis in A375 cells in a dose-dependent manner through a caspase-dependent, mitochondria-mediated pathway. While most Bcl-2 family proteins were unaffected, 9(11)-DHEP significantly downregulated the anti-apoptotic protein Mcl-1. The mechanism involved cytochrome c release and activation of caspase-3, -7, and -9.

Conclusion

The study demonstrates that 9(11)-DHEP induces apoptosis in melanoma cells through downregulation of Mcl-1, leading to mitochondrial membrane damage, cytochrome c release, and caspase activation. These findings suggest 9(11)-DHEP may be a promising natural compound for melanoma treatment by targeting Mcl-1-dependent survival pathways.

Published in:Molecular Medicine Reports,
Study Type:Laboratory Research,
Source: 10.3892/mmr.2018.9035