{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:08:23Z","timestamp":1770800903259,"version":"3.50.0"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Drugs and Vaccines from the Sea","award":["PG\/2018\/0494374"],"award-info":[{"award-number":["PG\/2018\/0494374"]}]},{"name":"\u201cFattoria La Vialla di Gianni, Antonio e Bandino Lo Franco\u2014SAS\u201d","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"IEO-MONZINO Foundation","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"IRCCS IEO","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"Italian Ministry of Health Ricerca Corrente\u2013IRCCS IEO","award":["-"],"award-info":[{"award-number":["-"]}]},{"name":"IRCCS MultiMedica","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Algal carotenoids play a promising role in handling chronic diseases due to their diverse bioactive properties, including anti-inflammatory, antioxidant, and anticancer effects. This study assesses the activity of the antioxidant xanthophyll diatoxanthin (Dt), derived from marine diatoms, against triple-negative breast cancer (TNBC) cells using in vitro models, gene expression evaluation, and explores its role in potentiating the cytotoxic effect of chemotherapy. Dt exhibited selective activity against MDA-MB-231 and BT-549 TNBC cells at concentrations \u226512.5 ng\/mL, with maximal effects observed at 25 ng\/mL while sparing human umbilical vein endothelial cells (HUVECs) at these doses. When combined with doxorubicin (0.1\u20130.5 \u03bcM), Dt enhanced the anti-tumor efficacy in both TNBC cell lines, further reducing cell viability compared with doxorubicin alone (p &lt; 0.05\u20130.001). Dt also exerted its activity in inhibiting migration and chemotaxis by approximately 30\u201350% compared with the controls (p &lt; 0.01) and suppressing 3D-tumor spheroid growth at day 12 (up to &gt;50% reduction, p &lt; 0.001). Notably, secretome analysis revealed Dt-induced changes in inflammatory, oxidative and angiogenic mediators, highlighting its ability to modulate the TNBC microenvironment. Dt also downregulated key pro-survival, pro-angiogenic and pro-tumorigenic genes in both TNBC cell lines, supporting its role in disrupting oncogenic pathways. Angiogenesis-related genes were significantly reduced. Dt also decreased the expression of angiogenic mediators in HUVECs, supporting Dt\u2019s role in inhibiting tumor vascularization. Results on gene expression regulation were also confirmed by RNA-Seq analysis. These findings pose Dt as a promising chemopreventing candidate in the challenging fight against TNBC, a well-known type of cancer that is aggressive and resistant to conventional therapies, targeting critical pathways for tumor survival, such as inflammation, angiogenesis, tumor cell growth, and cell migration. Given its selective activity against TNBC cells, ability to enhance chemotherapy efficacy, and modulation of the tumor microenvironment, Dt holds promise as a complementary drug for cancer prevention and interception. Future studies should focus on validating these effects in vivo and exploring Dt\u2019s potential in combinatorial treatment strategies for cancer.<\/jats:p>","DOI":"10.3390\/antiox15020205","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T13:56:23Z","timestamp":1770213383000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Algal Antioxidant Carotenoid Diatoxanthin as a Modulator of Inflammation and Angiogenesis in Triple-Negative Breast Cancer Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Danilo","family":"Morelli","sequence":"first","affiliation":[{"name":"Fondazione IRCCS Istituto Tumori di Milano, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3680-8821","authenticated-orcid":false,"given":"Luana","family":"Calabrone","sequence":"additional","affiliation":[{"name":"ISB\u2014Ion Source & Biotechnologies Srl, 20017 Rho, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5329-8689","authenticated-orcid":false,"given":"Luisa","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Unit of Chemical-Physics Fundamentals in Chemical Engineering, Department of Science and Technology, Universit\u00e0 Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9502-6400","authenticated-orcid":false,"given":"Giovanna","family":"Chiorino","sequence":"additional","affiliation":[{"name":"Lab of Cancer Genomics, Fondazione Edo ed Elvo Tempia, 13900 Biella, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-2954","authenticated-orcid":false,"given":"Paola","family":"Ostano","sequence":"additional","affiliation":[{"name":"Lab of Cancer Genomics, Fondazione Edo ed Elvo Tempia, 13900 Biella, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8058-0719","authenticated-orcid":false,"given":"Douglas M.","family":"Noonan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"},{"name":"Unit of Molecular Pathology, Biochemistry and Immunology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), MultiMedica, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9269-0146","authenticated-orcid":false,"given":"Giovanni","family":"Corso","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy"},{"name":"Department of Oncology and Hematology, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9624-5103","authenticated-orcid":false,"given":"Adriana","family":"Albini","sequence":"additional","affiliation":[{"name":"Scientific Directorate, European Institute of Oncology (IEO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20141 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural products as sources of new drugs over the nearly four decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. 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