Psoralen induced cell cycle arrest by modulating Wnt/β-catenin pathway in breast cancer cells

Area of Science:

• Pharmacology
• Oncology
• Molecular Biology

Background:

• Psoralen's anti-proliferative effects on breast cancer cells are known, but the underlying molecular mechanisms remain largely unelucidated.
• Understanding these mechanisms is crucial for exploring psoralen as a potential therapeutic agent for breast cancer.

Purpose of the Study:

• To investigate the molecular mechanisms by which psoralen inhibits human breast cancer cell proliferation.
• To evaluate the impact of psoralen on the Wnt/β-catenin signaling pathway and its downstream targets in breast cancer cells.
• To assess the in vivo anti-tumor efficacy and potential toxicity of psoralen in a mouse model.

Main Methods:

• Cell proliferation was assessed using MTT assays, colony formation assays, and cell cycle analysis in MCF-7 and MDA-MB-231 cell lines.
• Wnt/β-catenin pathway activation and target gene expression were analyzed via quantitative real-time PCR, western blotting, and immunofluorescence.
• In vivo studies involved monitoring tumor growth in BALB/c nude mice and examining organ pathology.

Main Results:

• Psoralen induced G0/G1 phase arrest in MCF-7 cells and G2/M phase arrest in MDA-MB-231 cells, significantly inhibiting proliferation.
• Psoralen treatment reduced Fra-1 expression and increased Axin2 expression in both cell lines.
• The compound suppressed cytoplasmic accumulation and nuclear translocation of β-catenin, decreased total β-catenin, and increased phospho-(Y142) β-catenin levels.
• In vivo studies confirmed anti-tumor effects without significant cardiotoxicity, hepatotoxicity, or nephrotoxicity.

Conclusions:

• Psoralen inhibits breast cancer cell proliferation through cell cycle arrest and modulation of the Wnt/β-catenin pathway.
• Psoralen reduces β-catenin signaling and its downstream target Fra-1, offering a potential therapeutic strategy.
• The findings support the potential clinical application of psoralen in breast cancer treatment due to its efficacy and safety profile.