{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T20:16:27Z","timestamp":1781122587293,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:00:00Z","timestamp":1759968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Gastric cancer remains a major global health burden with limited therapeutic options due to resistance and toxicity of current treatments. Marine red algae\u2014\n                      <jats:italic>Gracilaria edulis<\/jats:italic>\n                      ,\n                      <jats:italic>Eucheuma denticulatum<\/jats:italic>\n                      ,\u00a0and\u00a0\n                      <jats:italic>Kappaphycus striatus<\/jats:italic>\n                      \u2014are underexplored sources of bioactive compounds that may offer multi\u2010targeted, low\u2010toxicity agents for gastric cancer therapy. This study integrated phytochemical profiling, structure\u2013activity relationship (SAR) analysis, network pharmacology, molecular docking, molecular dynamics simulations, and in vitro validation. SAR and docking analyses showed strong affinities of key compounds, including camptothecin and 24(S),25\u2010epoxycholesterol, with gastric cancer targets (PTGER3, TGFBR1, IGF1R, CDK6, BRD4). Molecular dynamics confirmed the stability of camptothecin\u2013TGFBR1 interactions.\u00a0\n                      <jats:italic>Kappaphycus striatus<\/jats:italic>\n                      \u00a0extract (KSE) significantly downregulated TGF\u2010\u03b21 expression in MKN\u201045 cells in a dose\u2010dependent manner. Cytotoxicity assays demonstrated that KSE, camptothecin, and 24(S),25\u2010epoxycholesterol selectively inhibited AGS and MKN\u201045 gastric cancer cells while sparing normal epithelial cells. The findings highlight Indonesian red algae as promising, safe, and sustainable sources of multi\u2010targeted anti\u2010gastric cancer agents. In particular, KSE and its bioactive constituents exhibit both cytotoxic and epigenetic modulatory effects, underscoring their potential for future therapeutic development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mnfr.70282","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T05:54:40Z","timestamp":1760075680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Integrative Pharmacoinformatic and Experimental Validation of Indonesian Red Algae as Novel Functional Food for Anti\u2010Gastric Cancer Agents"],"prefix":"10.1002","volume":"69","author":[{"given":"Fahrul","family":"Nurkolis","sequence":"first","affiliation":[{"name":"Master of Basic Medical Science Faculty of Medicine, Universitas Airlangga  Surabaya Indonesia"},{"name":"State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga)  Yogyakarta Indonesia"},{"name":"Medical Research Center of Indonesia  Surabaya Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan Maitri","family":"Aldian","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Airlangga  Surabaya Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky Indra","family":"Alfaray","sequence":"additional","affiliation":[{"name":"Medical Research Center of Indonesia  Surabaya Indonesia"},{"name":"Faculty of Medicine Universitas Airlangga  Surabaya Indonesia"},{"name":"Department of Environmental and Preventive Medicine Faculty of Medicine, Oita University  Oita Japan"},{"name":"Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga  Surabaya Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abu Rizal Dwikatmono","family":"Johan","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Universitas Airlangga  Surabaya Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andri","family":"Frediansyah","sequence":"additional","affiliation":[{"name":"Research Center for Food Technology and Processing (PRTPP) National Research and Innovation Agency (BRIN)  Yogyakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Happy Kurnia","family":"Permatasari","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomolecular Faculty of Medicine, Universitas Brawijaya  Malang Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurpudji Astuti","family":"Taslim","sequence":"additional","affiliation":[{"name":"Division of Clinical Nutrition Department of Nutrition Faculty of Medicine Hasanuddin University  Makassar Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond Rubianto","family":"Tjandrawinata","sequence":"additional","affiliation":[{"name":"Center For Pharmaceutical and Nutraceutical Research and Policy Faculty of Biotechnology Atma Jaya Catholic University of Indonesia  Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arifa","family":"Mustika","sequence":"additional","affiliation":[{"name":"Department of Anatomy Histology, and Pharmacology, Faculty of Medicine, Universitas Airlangga  Surabaya Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonglee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology College of Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Santini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Miftahussurur","sequence":"additional","affiliation":[{"name":"Helicobacter Pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga  Surabaya Indonesia"},{"name":"Division of Gastroentero\u2010Hepatology Department of Internal Medicine Faculty of Medicine\u2014Dr. Soetomo Teaching Hospital, Universitas Airlangga  Surabaya Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.18457"},{"key":"e_1_2_11_3_1","first-page":"78","volume":"21","author":"Tan N.","year":"2024","journal-title":"Cancer Biology and Medicine"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00703-w"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25194411"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1515\/jcim\u20102019\u20100203"},{"key":"e_1_2_11_7_1","first-page":"1","author":"Carpena M.","year":"2022","journal-title":"Phytochemistry Reviews"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rsma.2020.101499"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/md19100531"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e04654"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11172-017-1954-x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2021.1959318"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.7324\/japs.2021.120208"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky318"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","unstructured":"M.Dunkel S.G\u00fcnther J.Ahmed B.Wittig andR.Preissner \u201cSuperPred: Drug Classification and Target Prediction \u201dNucleic Acids Research36(2008): W55\u20139.","DOI":"10.1093\/nar\/gkn307"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1000"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-128"},{"key":"e_1_2_11_18_1","doi-asserted-by":"crossref","unstructured":"M. V.Kuleshov M. R.Jones A. D.Rouillard et\u00a0al. \u201cEnrichr: A Comprehensive Gene Set Enrichment Analysis Web Server 2016 Update \u201dNucleic Acids Research44(2016): W90\u20137.","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.90"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac394"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac087"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-78464-6"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","unstructured":"S.Kim P. A.Thiessen E. E.Bolton et\u00a0al. \u201cPubChem Substance and Compound databases \u201dNucleic Acids Research44(2016): D1202\u201313.","DOI":"10.1093\/nar\/gkv951"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005659"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22711"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-5-367"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prmcm.2024.100551"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jafr.2024.101526"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jafr.2024.101362"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28031365"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28073267"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092301"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013\u2010025\u201001685\u20107"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-020-01455-0"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.4c00597"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10811-022-02863-3"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10811-021-02482-4"},{"key":"e_1_2_11_38_1","first-page":"2199","volume":"7","author":"Yen E.\u2010Y.","year":"2017","journal-title":"American Journal of Cancer Research"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3727\/096504016X14570992647203"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14225682"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154038"},{"key":"e_1_2_11_42_1","author":"Janani G.","year":"2025","journal-title":"Chemistry and Biodiversity"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29092077"}],"container-title":["Molecular Nutrition &amp; Food Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mnfr.70282","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:05:48Z","timestamp":1764587148000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mnfr.70282"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,9]]},"references-count":42,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/mnfr.70282"],"URL":"https:\/\/doi.org\/10.1002\/mnfr.70282","archive":["Portico"],"relation":{},"ISSN":["1613-4125","1613-4133"],"issn-type":[{"value":"1613-4125","type":"print"},{"value":"1613-4133","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,9]]},"assertion":[{"value":"2025-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70282"}}