{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:30Z","timestamp":1785409830184,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"crossref","award":["63243138"],"award-info":[{"award-number":["63243138"]}],"id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"crossref","award":["BB042412"],"award-info":[{"award-number":["BB042412"]}],"id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"crossref"}]},{"award":["63243138"],"award-info":[{"award-number":["63243138"]}],"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BB042412"],"award-info":[{"award-number":["BB042412"]}],"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}]},{"name":"\u201cDatabase of Coastal Bioresources of China\u201d in National Basic Science Data Center","award":["NBSDC-DB-22"],"award-info":[{"award-number":["NBSDC-DB-22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Lectins are carbohydrate-binding proteins, some of which exhibit significant anti-tumor activity. Siye is a lectin derived from the red alga Kappaphycus alvarezii that was previously discovered using an artificial intelligence-guided genome mining strategy and shown to exert cytotoxic effects against several human cancer cell lines, including breast adenocarcinoma HCC1937. Based on the presence of shared glycopatterns between breast and colon cancers, we hypothesized that Siye may also exhibit anti-tumor activity against colon cancer cells. The cytotoxic effect of Siye on human colon cancer HCT116 cells was evaluated using the CCK-8 assay. Apoptosis was assessed by flow cytometry with Annexin V-FITC\/PI staining. Expression levels of apoptosis-related genes (Bax, Bcl-2, Casp3, Casp8, Casp9, and TP53) were determined by qRT-PCR. Competitive inhibition assays using mannan were performed to assess the role of cell surface glycan binding. Siye significantly reduced the viability of HCT116 cells in a dose-dependent manner, with an IC50 value of 14.065 \u03bcg\/mL (=0.488 \u03bcM). Flow cytometry revealed that Siye promoted both early and late apoptosis in HCT116 cells, whereas in HCC1937 cells, the effect was primarily on early apoptosis. Mechanistically, Siye significantly upregulated the expression of the pro-apoptotic genes Bax (p &lt; 0.05) and Casp9 (p &lt; 0.001) in HCT116 cells, while in HCC1937 cells, Casp9 expression was significantly increased (p &lt; 0.001). Morphological changes, including cell rounding and agglutination, were observed within 4 h of Siye treatment in both cell lines and were attenuated by co-treatment with mannan, suggesting that Siye-induced morphological changes are associated with binding to cell surface glycans. This study suggests that the red algal lectin Siye exerts anti-tumor effects against colon cancer HCT116 cells by inducing caspase-associated apoptosis. The differential apoptotic response between HCC1937 and HCT116 cells suggests cell-type-specific mechanisms. These findings extend the known anti-tumor activity spectrum of AI-discovered red algal lectin Siye and provide a basis for further investigation of its glycan-associated cellular effects and marine drug discovery potential.<\/jats:p>","DOI":"10.3390\/md24060199","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T11:52:30Z","timestamp":1780573950000},"page":"199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect of Algal Lectin Siye on Proliferation and Apoptosis of Breast and Colon Cancer Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3542-4160","authenticated-orcid":false,"given":"Xiaobo","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China"},{"name":"College of Life Science, Nankai University, Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7239-1560","authenticated-orcid":false,"given":"Jiahao","family":"Ma","sequence":"additional","affiliation":[{"name":"BayVax Biotech Limited, 17 Science Park West Avenue, Hong Kong Science Park, Shatin, Hong Kong SAR, China"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China"},{"name":"Materials Innovation Institute for Life Sciences and Energy, The University of Hong Kong, 1 Honghua Road, Shenzhen 518016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongli","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Coastal Biology and Biological Resource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianfeng","family":"Ruan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyu","family":"Pang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1654-3259","authenticated-orcid":false,"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102962","DOI":"10.1016\/j.algal.2022.102962","article-title":"Antitumor lectins from algae: A systematic review","volume":"70","author":"Cavalcanti","year":"2023","journal-title":"Algal Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Lee, S.B., Kim, H., Shin, J.M., Yoon, M., An, H.S., and Han, J.W. 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