{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:03:43Z","timestamp":1792569823593,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Top Discipline of Biological Engineering","award":["KF2022010"],"award-info":[{"award-number":["KF2022010"]}]},{"name":"Zhejiang Provincial Top Discipline of Biological Engineering","award":["CX2024037"],"award-info":[{"award-number":["CX2024037"]}]},{"name":"College Students\u2019 Innovation and Entrepreneurship Training Program","award":["S202410876082"],"award-info":[{"award-number":["S202410876082"]}]},{"name":"Natural Science Foundation of Ningbo City","award":["2023J294"],"award-info":[{"award-number":["2023J294"]}]},{"name":"Natural Science Foundation of Ningbo City","award":["2024J249"],"award-info":[{"award-number":["2024J249"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Fucoxanthin, a marine carotenoid abundantly derived from brown algae, has been increasingly recognized for its broad-spectrum antitumor activities; however, its role in regulating ferroptosis remains insufficiently defined. Hypopharyngeal carcinoma is a highly aggressive head and neck malignancy with limited therapeutic options, highlighting the need for novel marine-derived anticancer agents. In this study, we investigated whether fucoxanthin induces ferroptosis in human hypopharyngeal carcinoma cells (Fadu) and elucidated the underlying molecular mechanisms. Transcriptome profiling combined with in vitro validation revealed that fucoxanthin markedly upregulated heme oxygenase\u22121 (HO\u22121), leading to increased intracellular Fe2+ levels, excessive reactive oxygen species (ROS) generation, and pronounced lipid peroxide accumulation. Fucoxanthin simultaneously reduced cysteine and glutathione (GSH) levels, disrupted mitochondrial membrane potential, and triggered ferroptotic cell death, which was significantly reversed by the ferroptosis inhibitor ferrostatin\u22121. Mechanistically, fucoxanthin activated the p53 pathway while suppressing SLC7A11 and GPX4, thereby impairing antioxidant defenses. Pharmacological inhibition of p53 with Pifithrin\u2212\u03b1 markedly attenuated fucoxanthin-induced cytotoxicity and ferroptosis. Together, these findings identify fucoxanthin as a promising marine-derived compound capable of inducing ferroptosis via modulation of the p53\/SLC7A11\/GPX4 axis, providing new insights into its potential application in hypopharyngeal carcinoma therapy.<\/jats:p>","DOI":"10.3390\/md24020055","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T17:07:38Z","timestamp":1769533658000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fucoxanthin Induces Ferroptosis in Hypopharyngeal Carcinoma Cells by Activating the p53\/SLC7A11\/GPX4 Axis"],"prefix":"10.3390","volume":"24","author":[{"given":"Yingxing","family":"Xie","sequence":"first","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"},{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3911-7574","authenticated-orcid":false,"given":"Haofei","family":"Du","sequence":"additional","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"},{"name":"School of Food Science and Engineering, Hainan University, Haikou 570228, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sihan","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying","family":"Qian","sequence":"additional","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"},{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3846-7701","authenticated-orcid":false,"given":"Haomiao","family":"Ding","sequence":"additional","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"},{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2411-8675","authenticated-orcid":false,"given":"Caisheng","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"ref_1","first-page":"470","article-title":"Smoking and head and neck cancer","volume":"149","author":"Yu","year":"2023","journal-title":"JAMA Otolaryngol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/s42003-025-07700-0","article-title":"Multi-omics insights into the molecular signature and prognosis of hypopharyngeal squamous cell carcinoma","volume":"8","author":"Ren","year":"2025","journal-title":"Commun. 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