Research antioxidant properties of natural and synthetic polyphenols

Onychina, K. K.; Radosteva, Ekaterina; Газизуллина, Е. Р.; Gerasimova, E. L.; Шарафутдинова, Е. Н.; Иванова, А. В.

doi:10.1063/5.0069285

Cited by 1 publication

(1 citation statement)

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“…However, one of the main challenges and limitations in the use of polyphenols as chemotherapy adjuvants consists of their poor bioavailability due to their high metabolism rate and quick bodily removal [76]. Thus, the research is now focused on the synthesis of polyphenol-derived compounds to harness their beneficial effects on human health while overcoming this issue [77][78][79].…”

Section: Discussionmentioning

confidence: 99%

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

Perta,

Torrieri Di Tullio,

Cugini

et al. 2023

Biology

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Polyphenols have gained increasing attention for their therapeutic potential, particularly in conditions like cancer, due to their established antioxidant and anti-inflammatory properties. Recent research highlights their ability to bind to transition metals, such as copper. This is particularly noteworthy given the key role of copper both in the initiation and progression of cancer. Copper can modulate the activity of kinases required for the epithelial–mesenchymal transition (EMT), a process fundamental to tumor cell dissemination. We have previously demonstrated the copper-binding capacity of oleuropein, a secoiridoid found in Olea europaea. In the present study, we investigated the effect of hydroxytyrosol, the primary oleuropein metabolite, on the metastatic potential of three triple-negative breast cancer cell lines (MDA-MB-231, MDA-MB-468, and SUM159). We found that hydroxytyrosol modulated the intracellular copper levels, influencing both the epithelial and mesenchymal markers, by downregulating copper-dependent AKT phosphorylation, a member of the EMT signaling cascade, through Western blot, RT-qPCR, and immunofluorescence. Indeed, by optical spectra, EPR, and in silico approaches, we found that hydroxytyrosol formed a complex with copper, acting as a chelating agent, thus regulating its homeostasis and affecting the copper-dependent signaling cascades. While our results bring to light the copper-chelating properties of hydroxytyrosol capable of countering tumor progression, they also provide further confirmation of the key role of copper in promoting the aggressiveness of triple-negative breast cancer cells.

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