{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T10:16:23Z","timestamp":1783678583967,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Council of Humanities, Sciences and Technologies (CONAHCYT), Mexico","award":["388785"],"award-info":[{"award-number":["388785"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, and the efficacy of conventional chemotherapy is frequently limited by systemic toxicity, chemoresistance, and tumor recurrence. Natural products derived from marine algae and plants have attracted increasing interest as multitarget adjuvant agents capable of modulating apoptosis, oxidative stress, and tumor-associated signaling pathways. In the present study, we evaluated the anticancer activity of commercially available formulations enriched in fucoxanthin, fucoidan, tocotrienols, astaxanthin, and apple polyphenols, either alone or in combination with doxorubicin (DOX), using two-dimensional and three-dimensional colorectal cancer models. Initial IC50 screening in ovarian (OVCAR3), prostate (PC3), colorectal (Caco2 and HT-29), and non-tumorigenic colon epithelial cells demonstrated that formulations 2.1 and 10.0 exhibited the most relevant cytotoxic activity, particularly in colorectal cancer cells. Combined treatments with DOX significantly reduced cell viability compared to individual treatments, particularly in Caco2 cells, where viability decreased to approximately 10% under combined exposure conditions. Mechanistically, combined treatments enhanced caspase-3\/7 activation in both Caco2 and HT-29 cells, indicating apoptosis-associated effects. These findings were further supported in three-dimensional spheroid models, where supplement combinations impaired spheroid expansion, induced apoptotic AO\/EB staining patterns, and reduced HT-29 spheroid growth by approximately 30\u201335%, reaching inhibitory effects comparable to DOX alone. Collectively, these results suggest that plant- and algae-derived formulations enriched in antioxidant bioactives may enhance chemotherapy-associated antitumor responses through apoptosis-related mechanisms and modulation of tumor-like growth behavior. The present findings support the further exploration of natural-product-based adjuvant strategies in colorectal cancer therapy using more clinically representative chemotherapeutic schemes and in vivo models.<\/jats:p>","DOI":"10.3390\/molecules31142414","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:50:56Z","timestamp":1783587056000},"page":"2414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plant- and Algae-Derived Compounds Enhance the Anticancer Activity of Doxorubicin in Colorectal Cancer Cell Lines"],"prefix":"10.3390","volume":"31","author":[{"given":"Jos\u00e9 Alberto","family":"Ramos-Silva","sequence":"first","affiliation":[{"name":"Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Facultad de Ciencias Biol\u00f3gicas, Instituto de Biotecnolog\u00eda, Av. Uni-versidad S\/N, San Nicol\u00e1s de los Garza 66455, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Lara-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Simbio Health Sapi de CV, San Jos\u00e9 249, Tlajomulco de Z\u00fa\u00f1iga 45645, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Fuentes-Garibay","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Facultad de Ciencias Biol\u00f3gicas, Instituto de Biotecnolog\u00eda, Av. Uni-versidad S\/N, San Nicol\u00e1s de los Garza 66455, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-0825","authenticated-orcid":false,"given":"Elvia","family":"P\u00e9rez-Soto","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomedicina y Salud Ocupacional, Escuela Nacional de Medicina y Homeopat\u00eda, Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ericka Patricia","family":"Flores-Berrios","sequence":"additional","affiliation":[{"name":"Investigaci\u00f3n y Desarrollo, Biodesarrollos Valmex, Circuito Crisantemos 10, Tlajomulco de Zu\u00f1iga 45640, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6813-6869","authenticated-orcid":false,"given":"Hamlet","family":"Avil\u00e9s-Arnaut","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Nuevo Le\u00f3n, Facultad de Ciencias Biol\u00f3gicas, Instituto de Biotecnolog\u00eda, Av. Uni-versidad S\/N, San Nicol\u00e1s de los Garza 66455, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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