{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:51:50Z","timestamp":1787784710416,"version":"build-2784847793"},"reference-count":84,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2020-NR055141"],"award-info":[{"award-number":["RS-2020-NR055141"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS-2023-KH139660"],"award-info":[{"award-number":["RS-2023-KH139660"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Background: Marine-derived secondary metabolites such as phlorotannins from the edible brown alga Ecklonia cava exhibit diverse bioactivities. However, their mechanisms in inflammation-associated cancer remain insufficiently understood. Methods: This study explored the anticancer potential of three major phlorotannins (dieckol, 7-phloroeckol, and 8,8\u2032-bieckol) through network pharmacology, molecular docking, molecular dynamics simulations, and in vitro validation in SKOV3 ovarian cancer cells and tumor-associated macrophages (TAMs). Results: Computational analyses revealed stable binding of phlorotannins to IL-17RA, with 7-phloroeckol and 8,8\u2032-bieckol preferentially engaging loop-proximal regions of the receptor, while dieckol interacted with spatially distinct residues. In SKOV3 ovarian cancer cells, phlorotannins suppressed migration and invasion by approximately 40 to 60%, accompanied by reduced MMP expression linked to IL-17RA\u2013Act1 signaling attenuation and by increased TIMP1 expression in association with transient ERK1\/2 activation. In TAMs, phlorotannins attenuated pro-tumorigenic cytokine production and polarization marker expression, indicating suppression of tumor-supportive immune activity. Conclusions: Collectively, these findings demonstrate that E. cava-derived phlorotannins exert anti-metastatic effects through dual regulation of IL-17RA\/Act1 and ERK1\/2 signaling pathways, offering mechanistic insight into their therapeutic potential against inflammation-driven malignancies.<\/jats:p>","DOI":"10.3390\/md24010012","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T16:41:19Z","timestamp":1766594479000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phlorotannins from Ecklonia cava Regulate Dual Signaling Pathways, IL-17RA\/Act1 and ERK1\/2, to Suppress Ovarian Cancer Progression and Tumor-Associated Macrophage Activation"],"prefix":"10.3390","volume":"24","author":[{"given":"Eun-Hye","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Korean Pharmacy, Woosuk University, Wanju 55338, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hwi-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Korean Pharmacy, Woosuk University, Wanju 55338, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-6814","authenticated-orcid":false,"given":"Jung-Hye","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0750-5648","authenticated-orcid":false,"given":"Ji-Hye","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Korean Pharmacy, Woosuk University, Wanju 55338, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00432-014-1819-8","article-title":"Dieckol, isolated from the edible brown algae Ecklonia cava, induces apoptosis of ovarian cancer cells and inhibits tumor xenograft growth","volume":"141","author":"Ahn","year":"2015","journal-title":"J. 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