{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T13:38:20Z","timestamp":1789133900232,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Natural Science Foundation of Guangdong Province, China","award":["2023A1515012637"],"award-info":[{"award-number":["2023A1515012637"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Galectin-3 (Gal-3) is a histologic marker of pancreatic cancer and a potential therapeutic target. This study aimed to characterize a novel sulfated agarose-derived oligosaccharide (DP9) from marine algae, Gracilaria lemaneiformis, evaluate its Gal-3 inhibitory activity, and investigate its anti-pancreatic cancer mechanisms. Through controlled acid hydrolysis, a series of odd-numbered oligosaccharides (DP3-11) were obtained, in which DP9 showed the strongest Gal-3 inhibition in hemagglutination assays. Structural analysis confirmed DP9\u2019s unique composition including an alternating \u03b2 (1\u21924)-D-galactose and \u03b1 (1\u21923)-3,6-anhydro-L-galactose backbone, featuring partial 6-O-methylation on \u03b2-D-galactose and 6-O-sulfation on 3,6-anhydro-\u03b1-L-galactose residues. Molecular docking revealed DP9\u2019s binding to Gal-3\u2019s carbohydrate recognition domain through key hydrogen bonds (His158, Arg162, Lys176, Asn179 and Arg186) and hydrophobic interactions (Pro117, Asn119, Trp181 and Gly235), with the sulfate group enhancing binding affinity. In vitro studies demonstrated DP9\u2019s selective anti-pancreatic cancer activity against BxPC-3 cells, including inhibition of cell proliferation; S-phase cell cycle arrest; induction of apoptosis; and suppression of migration and invasion. Mechanistically, DP9 attenuated the Gal-3\/EGFR\/AKT\/FOXO3 signaling pathway while showing minimal cytotoxicity to normal cells. This study first demonstrated that agarose-derived odd-numbered oligosaccharides (DP9) can serve as effective Gal-3 inhibitors, which proved its potential as a marine oligosaccharide-based therapeutic agent for pancreatic cancer.<\/jats:p>","DOI":"10.3390\/md23110423","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T03:33:07Z","timestamp":1761881587000},"page":"423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Novel Sulfated Oligosaccharide DP9 from Marine Algae, Gracilaria lemaneiformis: A Potent Galectin-3 Inhibitor for Pancreatic Cancer Therapy"],"prefix":"10.3390","volume":"23","author":[{"given":"Pingting","family":"Liu","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Guangdong Engineering Technology Research Center of Offshore Environmental Pollution Control, Department of Biology, College of Science, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Guangdong Engineering Technology Research Center of Offshore Environmental Pollution Control, Department of Biology, College of Science, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicong","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Guangdong Engineering Technology Research Center of Offshore Environmental Pollution Control, Department of Biology, College of Science, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-471X","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Marine Biotechnology, Guangdong Engineering Technology Research Center of Offshore Environmental Pollution Control, Department of Biology, College of Science, Shantou University, Shantou 515063, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1023\/B:GLYC.0000014084.01324.15","article-title":"Galectin-3 and metastasis","volume":"19","author":"Takenaka","year":"2002","journal-title":"Glycoconj. 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