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KHZ (Fusion of Ganoderma lucidum and Polyporus umbellatus Mycelia) Induces Apoptosis by Increasing Intracellular Calcium Levels and Activating JNK and NADPH Oxidase-Dependent Generation of Reactive Oxygen Species

Summary

This research investigated how a compound called Khz, made by fusing two medicinal mushrooms, can selectively kill cancer cells while leaving healthy cells unharmed. The study revealed the precise molecular mechanisms by which this compound works, showing promise for potential cancer treatment applications. Impacts on everyday life: • Demonstrates potential for developing natural anti-cancer treatments with fewer side effects • Shows how traditional medicinal mushrooms can be combined to create more effective treatments • Provides new understanding of how to target cancer cells specifically • Suggests possible development of new cancer therapies using mushroom-derived compounds

Background

Cancer develops from abnormal cellular proliferation or defects in apoptosis that lead to uncontrolled growth. Natural products that can induce cancer cell death without toxicity are being investigated as potential anticancer agents. Ganoderma lucidum and Polyporus umbellatus have shown anticancer effects individually, but their fusion product Khz had not been fully studied.

Objective

To investigate the mechanism by which Khz, a fusion product of Ganoderma lucidum and Polyporus umbellatus mycelia, induces cell death in cancer cells and identify the key signaling pathways involved in this process.

Results

Khz induced selective apoptosis in transformed cells while sparing non-transformed cells. The apoptosis was caspase-dependent and occurred through a mitochondrial pathway. Khz triggered a rapid increase in intracellular calcium levels, which activated JNK and led to NADPH oxidase-dependent ROS generation. This was followed by mitochondrial ROS production and ultimately cell death. The process required both NADPH oxidase and mitochondrial ROS generation, with NADPH oxidase acting as the initial trigger.

Conclusion

Khz induces mitochondria-mediated apoptosis preferentially in transformed cells through a signaling pathway involving increased intracellular calcium, JNK activation, and ROS generation via NADPH oxidase and mitochondria. This selective targeting of cancer cells suggests potential therapeutic applications.
  • Published in:PLoS One,
  • Study Type:Laboratory Research,
  • Source: 10.1371/journal.pone.0046208
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