Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties
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 not...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/11/1437 |
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| author | Nunzio Perta Laura Torrieri Di Tullio Elisa Cugini Paola Fattibene Maria Cristina Rapanotti Ilaria Borromeo Cinzia Forni Patrizia Malaspina Tiziana Cacciamani Daniele Di Marino Luisa Rossi Anastasia De Luca |
| author_facet | Nunzio Perta Laura Torrieri Di Tullio Elisa Cugini Paola Fattibene Maria Cristina Rapanotti Ilaria Borromeo Cinzia Forni Patrizia Malaspina Tiziana Cacciamani Daniele Di Marino Luisa Rossi Anastasia De Luca |
| author_sort | Nunzio Perta |
| collection | DOAJ |
| description | 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 <i>Olea europaea</i>. 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. |
| first_indexed | 2024-03-09T17:00:41Z |
| format | Article |
| id | doaj.art-7b8be866163d43daa529ed9e0b517f92 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T17:00:41Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-7b8be866163d43daa529ed9e0b517f922023-11-24T14:30:27ZengMDPI AGBiology2079-77372023-11-011211143710.3390/biology12111437Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing PropertiesNunzio Perta0Laura Torrieri Di Tullio1Elisa Cugini2Paola Fattibene3Maria Cristina Rapanotti4Ilaria Borromeo5Cinzia Forni6Patrizia Malaspina7Tiziana Cacciamani8Daniele Di Marino9Luisa Rossi10Anastasia De Luca11Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, ItalyIstituto Superiore di Sanità, Core Facilities, Viale Regina Elena, 299, 00185 Rome, ItalyDepartment of Laboratory Medicine, University of Rome Tor Vergata, Viale Oxford, 8, 00133 Rome, ItalyIstituto Superiore di Sanità, Core Facilities, Viale Regina Elena, 299, 00185 Rome, ItalyDepartment of Laboratory Medicine, University of Rome Tor Vergata, Viale Oxford, 8, 00133 Rome, ItalyPhD School in Evolutionary Biology and Ecology, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, ItalyDepartment of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, ItalyDepartment of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, ItalyPolyphenols 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 <i>Olea europaea</i>. 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.https://www.mdpi.com/2079-7737/12/11/1437polyphenolscopperepithelial to mesenchymal transitionAKTcopper complexEPR |
| spellingShingle | Nunzio Perta Laura Torrieri Di Tullio Elisa Cugini Paola Fattibene Maria Cristina Rapanotti Ilaria Borromeo Cinzia Forni Patrizia Malaspina Tiziana Cacciamani Daniele Di Marino Luisa Rossi Anastasia De Luca Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties Biology polyphenols copper epithelial to mesenchymal transition AKT copper complex EPR |
| title | Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties |
| title_full | Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties |
| title_fullStr | Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties |
| title_full_unstemmed | Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties |
| title_short | Hydroxytyrosol Counteracts Triple Negative Breast Cancer Cell Dissemination via Its Copper Complexing Properties |
| title_sort | hydroxytyrosol counteracts triple negative breast cancer cell dissemination via its copper complexing properties |
| topic | polyphenols copper epithelial to mesenchymal transition AKT copper complex EPR |
| url | https://www.mdpi.com/2079-7737/12/11/1437 |
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