{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:33:47Z","timestamp":1787567627797,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Greek Ministry of Development, Support for New Researchers with Emphasis on Young Researchers\u2014\u201c2nd Cycle\u2014Development of Human Resources, Education and Lifelong Learning\u201d Priority Axis 6","award":["MIS 5048983"],"award-info":[{"award-number":["MIS 5048983"]}]},{"name":"Peloponnese State District-National Recovery and Resilience Fund","award":["7-6-29-03"],"award-info":[{"award-number":["7-6-29-03"]}]},{"name":"World Olive Center for Health and the Leventis"},{"name":"Hellenic Pasteur Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: The health-protective properties of olive oil phenolics, including their potential chemopreventive and anticancer effects, have attracted considerable scientific interest. However, their in vivo efficacy and mechanisms of action remain insufficiently understood. Recent advances in extraction and purification technologies have enabled large-scale production of highly purified olive oil phenols and phenolic-rich extracts, facilitating translational research. Methods: Herein, the antitumor efficacy of isolated olive oil phenols and phenolic-rich formulations was investigated in an MDA-MB-231 triple-negative breast cancer (TNBC) xenograft model. Results: Intraperitoneal administration of oleocanthal (OLC), oleuropein aglycone (OleA) or their combination reduced endpoint tumor burden, with OLC exhibiting the most pronounced effect. Oral administration of total olive oil phenolics (OOPs) achieved comparable efficacy. Pre-treatment initiated before tumor cell implantation conferred the greatest protection, consistent with a prophylactic mode of action. In contrast, delayed intervention displayed diminished or no antitumor benefit. Phenolic-rich extra virgin olive oil likewise showed an inhibition trend in tumor progression. Mechanistically, OOPs attenuated plasma protein oxidation, modulated proteasome mediated proteolysis, and reduced \u03b3H2AX levels in vivo. Furthermore, OOPs negatively affected the MDA-MB-231 cell migration in a concentration-dependent manner in vitro. Conclusions: Collectively, these findings are consistent with antitumor activities of olive oil phenolics via multiple mechanisms and support their further investigation as prophylactic agents in TNBC and as nutraceuticals.<\/jats:p>","DOI":"10.3390\/nu18172756","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time-Dependent Multimechanistic Antitumor Effects of Olive Oil Phenolics in a Triple-Negative Breast Cancer Mouse Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Nikoleta Anna","family":"Madelou","sequence":"first","affiliation":[{"name":"Hellenic Pasteur Institute, 11521 Athens, Greece"},{"name":"Laboratory of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-6649","authenticated-orcid":false,"given":"Marianna","family":"Kapetanou","sequence":"additional","affiliation":[{"name":"Hellenic Pasteur Institute, 11521 Athens, Greece"},{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Papakonstantinou","sequence":"additional","affiliation":[{"name":"Hellenic Pasteur Institute, 11521 Athens, Greece"},{"name":"Laboratory of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7046-0481","authenticated-orcid":false,"given":"Olga","family":"Koutsoni","sequence":"additional","affiliation":[{"name":"Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zacharias","family":"Kakazanis","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Melliou","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-5344","authenticated-orcid":false,"given":"Prokopios","family":"Magiatis","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, 15771 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1026-577X","authenticated-orcid":false,"given":"Vasilis","family":"Zoumbourlis","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstathios S.","family":"Gonos","sequence":"additional","affiliation":[{"name":"Institute of Chemical Biology, National Hellenic Research Foundation, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2137-2340","authenticated-orcid":false,"given":"Haralabia","family":"Boleti","sequence":"additional","affiliation":[{"name":"Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41523-025-00741-y","article-title":"Dynamic HER2-Low Status among Patients with Triple Negative Breast Cancer (TNBC) and the Impact of Repeat Biopsies","volume":"11","author":"Bar","year":"2025","journal-title":"npj Breast Cancer"},{"key":"ref_2","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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