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Ganoderma lucidum induced apoptosis in NB4 human leukemia cells: involvement of Akt and Erk
Eva Calviño1, José Luis Manjón, Pilar Sancho
1Departamento de Bioquímica y Biología Molecular, Campus Universitario, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
Aim Of The Study:
The final goal of this work was to study the toxic and apoptosis effects induced by fractions from Ganoderma lucidum [Ganoderma lucidum (Curtis) P. Karst.; Ganodermataceae Donk] on NB4 human leukemia cells.
Materials And Methods:
Two aqueous extracts and a methanol-extracted column-chromatography semipurified fraction were obtained from Ganoderma lucidum fruiting body. Flow cytometry analyses were used to measure cell viability, cell cycle and DNA fragmentation and to quantify apoptosis. Western-blot analyses were used to quantify changes in apoptosis proteins and intracellular kinases.
Results:
Aqueous extracts slightly reduce cell viability and induce DNA fragmentation in NB4 cells. Methanol-extracted semipurified fraction at dilutions down to 15% or 40% of the initial fraction concentration reduced significantly the viability of these leukemia cells (treated for 19h) with induction of DNA fragmentation and induction of apoptosis. Overmore, the dilution down to 15% of the initial E3 concentration induced a reduction of p53 levels, of the Bcl2/Bax relationship as well as reduced levels of both unphosphorylated and phosphorylated Akt (Protein kinase Akt, protein kinase B) and Erk (Erk1 and 2).
Conclusions:
Induction of apoptosis and alterations in signal transduction kinases (Akt and Erk) are produced by active fractions from Ganoderma lucidum on human leukemia cells. These data could be of important relevance from the viewpoint of antitumor actions of compounds from Ganoderma lucidum. Eventual therapy applications in leukemia cells might be developed.
Insights
Fractions from Ganoderma lucidum induce apoptosis and reduce viability in human leukemia cells. These findings suggest potential antitumor applications for Ganoderma lucidum compounds in leukemia therapy.
Area of Science:
- Mycology
- Cell Biology
- Pharmacology
Background:
- Ganoderma lucidum (Curtis) P. Karst. is a mushroom with a history of medicinal use.
- NB4 human leukemia cells are a model for studying leukemia progression and treatment.
- Understanding the cytotoxic effects of natural compounds is crucial for drug discovery.
Purpose of the Study:
- To investigate the toxic and apoptosis-inducing effects of Ganoderma lucidum fractions on NB4 human leukemia cells.
- To identify specific molecular mechanisms underlying these effects.
Main Methods:
- Preparation of aqueous extracts and a methanol-extracted semipurified fraction from Ganoderma lucidum.
- Flow cytometry to assess cell viability, cell cycle, DNA fragmentation, and apoptosis.
- Western-blot analysis to quantify apoptosis-related proteins and intracellular kinases (Akt, Erk).
Main Results:
- Aqueous extracts showed mild reduction in cell viability and induced DNA fragmentation.
- The methanol-extracted semipurified fraction significantly reduced NB4 cell viability and induced apoptosis and DNA fragmentation.
- This fraction altered levels of p53, Bcl2/Bax ratio, and phosphorylated/unphosphorylated Akt and Erk.
Conclusions:
- Ganoderma lucidum fractions induce apoptosis in human leukemia cells.
- These fractions modulate key signaling pathways, including Akt and Erk kinases.
- The findings support the potential of Ganoderma lucidum compounds for developing novel leukemia therapies.
