{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:19:08Z","timestamp":1790104748227,"version":"4.0.1"},"reference-count":63,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008786","name":"Universidad Nacional Mayor de San Marcos","doi-asserted-by":"crossref","award":["B24100451"],"award-info":[{"award-number":["B24100451"]}],"id":[{"id":"10.13039\/501100008786","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008786","name":"Universidad Nacional Mayor de San Marcos","doi-asserted-by":"crossref","award":["B2010002m"],"award-info":[{"award-number":["B2010002m"]}],"id":[{"id":"10.13039\/501100008786","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) is known for being aggressive and potentially resistant to chemotherapy. This means that new ways to improve cancer treatments are a priority. So, the anticancer effect of binary combinations of fucoidan (FuLt) and the chemotherapeutic agents doxorubicin, paclitaxel, and 5-fluorouracil was evaluated. The Chou-Talalay combination index method was used to do this. This method allows the assessment of interactions between products by determining synergism, additive effect and antagonism with combination index &lt;1, =1 and &gt;1, respectively. Synergistic indices (SIs) were selected and applied to 4T1 homotypic spheroids. Oxidative stress caused by SIs was determined after 72 h by measuring the production of ROS and NO in both homotypic and heterotypic spheroids. Three SIs with an inhibitory effect of at least \u2265 0.50 and a dose reduction index &gt; 1 were selected. Considering the experimental and simulated SI, twelve, nineteen, and seven SIs were found for FuLt with doxorubicin, paclitaxel, and 5-fluorouracil, respectively. The highest levels of ROS and NO occurred at 12 and 72 h, respectively, in homotypic and heterotypic spheroids, indicating an immunomodulatory effect in heterotypic spheroids. These results suggest that the synergistic combination of FuLt with chemotherapeutic agents improves drug efficacy and modulates redox dynamics in 4T1 spheroids. Furthermore, FuLt alone exhibits cytotoxic properties.<\/jats:p>","DOI":"10.3390\/md23120451","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic Anticancer Activity of Fucoidan from Lessonia trabeculata Combined with Chemotherapeutic Agents in 4T1 Breast Spheroids"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2177-3462","authenticated-orcid":false,"given":"Rosa Mar\u00eda","family":"Condori Macuri","sequence":"first","affiliation":[{"name":"Research Group Immunomodulators and Antitumor of Natural and Synthetic Origen, Immunology Laboratory, Universidad Nacional Mayor de San Marcos, Lima 11-0058, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7425-7453","authenticated-orcid":false,"given":"Libertad","family":"Alzamora-Gonzales","sequence":"additional","affiliation":[{"name":"Research Group Immunomodulators and Antitumor of Natural and Synthetic Origen, Immunology Laboratory, Universidad Nacional Mayor de San Marcos, Lima 11-0058, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9759-288X","authenticated-orcid":false,"given":"Erasmo Honorio","family":"Colona-Vallejos","sequence":"additional","affiliation":[{"name":"Research Group Immunomodulators and Antitumor of Natural and Synthetic Origen, Immunology Laboratory, Universidad Nacional Mayor de San Marcos, Lima 11-0058, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3128-087X","authenticated-orcid":false,"given":"Raisa Teresa","family":"Cruz Riquelme","sequence":"additional","affiliation":[{"name":"Research Group Immunomodulators and Antitumor of Natural and Synthetic Origen, Immunology Laboratory, Universidad Nacional Mayor de San Marcos, Lima 11-0058, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9961-0938","authenticated-orcid":false,"given":"Laura In\u00e9s","family":"Pecho Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Research Group Immunomodulators and Antitumor of Natural and Synthetic Origen, Immunology Laboratory, Universidad Nacional Mayor de San Marcos, Lima 11-0058, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6407-5235","authenticated-orcid":false,"given":"Jherson Oscar","family":"Cisneros Gutierrez","sequence":"additional","affiliation":[{"name":"Research Group Immunomodulators and Antitumor of Natural and Synthetic Origen, Immunology Laboratory, Universidad Nacional Mayor de San Marcos, Lima 11-0058, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0181-301X","authenticated-orcid":false,"given":"Victor Alonso","family":"Montejo Anlas","sequence":"additional","affiliation":[{"name":"Research Group Immunomodulators and Antitumor of Natural and Synthetic Origen, Immunology Laboratory, Universidad Nacional Mayor de San Marcos, Lima 11-0058, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","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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