Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

Area of Science:

• Oncology
• Pharmacology
• Cell Biology

Background:

• Cancer stem-like cells (CS-like cells) drive breast cancer recurrence and drug resistance.
• Targeting CS-like cells is crucial for developing novel breast cancer therapeutics.
• Flubendazole, an FDA-approved anti-parasitic agent, presents a potential candidate for repurposing.

Purpose of the Study:

• To investigate the novel effects of flubendazole on breast CS-like cells.
• To evaluate flubendazole's potential as a therapeutic agent for breast cancer.

Main Methods:

• Assessed flubendazole's impact on breast cancer cell proliferation, mammosphere formation, and xenograft tumor growth.
• Analyzed the expression of stemness markers (CD44high/CD24low), self-renewal genes, and epithelial/mesenchymal markers.
• Investigated flubendazole's mechanism of action, including cell cycle progression and tubulin polymerization.
• Evaluated flubendazole's synergistic effects with fluorouracil and doxorubicin.

Main Results:

• Flubendazole inhibited breast cancer cell proliferation and delayed tumor growth in vivo.
• Flubendazole reduced the CD44high/CD24low subpopulation, suppressed mammosphere formation, and downregulated self-renewal genes.
• Flubendazole induced cell differentiation, inhibited migration, reduced mesenchymal markers, and increased epithelial markers.
• Flubendazole arrested cell cycle at G2/M phase by inhibiting tubulin polymerization and enhanced the cytotoxicity of conventional chemotherapeutics.

Conclusions:

• Flubendazole demonstrates significant efficacy in suppressing breast CS-like cells.
• Flubendazole inhibits key processes driving breast cancer progression, including proliferation, self-renewal, and migration.
• Flubendazole shows potential as a novel therapeutic agent for breast cancer, possibly in combination with existing treatments.