Ganoderma lucidum extract (GLE) impairs breast cancer stem cells by targeting the STAT3 pathway

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Triple-negative breast cancer (TNBC) aggressiveness is linked to breast cancer stem cells (BCSCs).
• The STAT3 signaling pathway is implicated in BCSCs, but its role in TNBC is not fully understood.
• Ganoderma lucidum extract (GLE) possesses anticancer properties.

Purpose of the Study:

• To investigate the effect of Ganoderma lucidum extract (GLE) on breast cancer stem cells (BCSCs) in triple-negative breast cancer (TNBC).
• To elucidate the role of the STAT3 pathway in GLE's anti-BCSC activity in TNBC.

Main Methods:

• In vitro cell viability assays and Western blotting for STAT3, OCT4, NANOG, and SOX2 expression.
• Analysis of BCSC markers (ALDH1, CD44+/CD24-) and mammosphere formation.
• In vivo studies using TNBC preclinical animal tumor models to assess tumor volume and weight.

Main Results:

• GLE significantly reduced TNBC cell viability and downregulated total and phosphorylated STAT3 expression.
• GLE decreased the expression of stem cell markers OCT4, NANOG, and SOX2, and reduced the BCSC population.
• GLE treatment led to the deformation of mammospheres and a significant reduction in tumor volume and weight in vivo.
• Analysis confirmed GLE's downregulation of the STAT3 pathway and stem cell markers within the BCSC compartment of tumors.

Conclusions:

• Ganoderma lucidum extract (GLE) exhibits anti-cancer activity against TNBC by targeting BCSCs.
• GLE exerts its effects through the downregulation of the STAT3 signaling pathway in BCSCs.
• These findings suggest GLE as a potential therapeutic agent for TNBC, specifically targeting the BCSC population.