Mulberry leaf extract inhibits cancer cell stemness in neuroblastoma

Area of Science:

• Oncology
• Cell Biology
• Natural Product Chemistry

Background:

• Cancer stem cells (CSCs) drive tumor growth and resistance to therapy.
• Existing treatments often fail to eradicate CSCs, necessitating novel therapeutic approaches.
• Neuroblastoma is a pediatric cancer with a significant unmet need for effective treatments targeting CSCs.

Purpose of the Study:

• To investigate the potential of mulberry leaf (ML) ethanolic extract to eliminate neuroblastoma stem cell-like populations.
• To determine the mechanisms by which ML extract affects CSC characteristics and signaling pathways.

Main Methods:

• Treatment of neuroblastoma stem cells with varying concentrations of ML extract.
• Assessment of cell differentiation, clonogenicity, and sphere formation.
• Analysis of stem cell and differentiation marker expression.
• Evaluation of the role of delta-like 1 homologue and the MEK/ERK pathway.

Main Results:

• ML extract (10-40 μg/ml) significantly enhanced neuroblastoma cell differentiation, indicated by neurite elongation and reduced clonogenicity.
• ML extract decreased the expression of stem cell markers and increased differentiation markers.
• Knock-down of delta-like 1 homologue potentiated the inhibitory effects of ML extract on colony formation.
• ML extract increased extracellular signal-regulated kinase (ERK) phosphorylation, which was blocked by MEK/ERK inhibitors.

Conclusions:

• Mulberry leaf extract exhibits chemopreventive effects against neuroblastoma by inhibiting CSC characteristics.
• ML extract regulates key CSC pathways, including the MEK/ERK signaling cascade.
• These findings suggest ML extract as a potential therapeutic option for neuroblastoma, targeting cancer stem cells.