Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Polyphenols exhibit therapeutic potential in cancer due to antioxidant and anti-inflammatory properties.
• Copper plays a critical role in cancer initiation, progression, and metastasis.
• Copper influences kinase activity essential for epithelial-mesenchymal transition (EMT), a key process in tumor cell dissemination.

Purpose of the Study:

• To investigate the effect of hydroxytyrosol, a metabolite of oleuropein, on the metastatic potential of triple-negative breast cancer (TNBC) cells.
• To elucidate the mechanism by which hydroxytyrosol impacts copper homeostasis and related signaling pathways in TNBC.

Main Methods:

• Utilized three TNBC cell lines (MDA-MB-231, MDA-MB-468, SUM159).
• Employed Western blot, RT-qPCR, and immunofluorescence to assess epithelial and mesenchymal markers and AKT phosphorylation.
• Applied optical spectra, Electron Paramagnetic Resonance (EPR), and in silico approaches to confirm hydroxytyrosol-copper complex formation.

Main Results:

• Hydroxytyrosol modulated intracellular copper levels in TNBC cells.
• Hydroxytyrosol downregulated copper-dependent AKT phosphorylation, a critical component of the EMT signaling cascade.
• Confirmed hydroxytyrosol acts as a copper-chelating agent, regulating copper homeostasis and impacting copper-dependent signaling.

Conclusions:

• Hydroxytyrosol possesses copper-chelating properties that can counteract tumor progression in triple-negative breast cancer.
• These findings highlight hydroxytyrosol's potential therapeutic role in managing aggressive breast cancers.
• Reinforces the significance of copper in promoting the aggressiveness of TNBC cells.