{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:23:13Z","timestamp":1787746993633,"version":"build-2784847793"},"reference-count":18,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>\n                    A\n                    <jats:sc>BSTRACT<\/jats:sc>\n                  <\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) remains a global health challenge. The efficacy of 5-fluorouracil (5-FU) is frequently limited by chemoresistance, inflammation, and compensatory pro-angiogenic signaling. Prebiotic fibers and metabolically active lipids have been shown to modulate immune-metabolic pathways that may influence tumor behavior and chemotherapy response. The aim of the study was to evaluate the immunomodulatory and chemo-adjunct effects of inulin, glucomannan, and a combined inulin\u2013glucomannan\u2013medium-chain triglyceride (MCT) formulation on CRC cells exposed to 5-FU. An\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    experimental study using human colorectal adenocarcinoma HT-29 cells. HT-29 cells were exposed to graded concentrations of inulin, glucomannan, or their combination with MCT, either as single treatments or combined with 5-FU. Outcomes included MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based viability, clonogenic survival, and vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) expression using immunocytochemical (ICC). Data differences were analyzed using one-way analysis of variance with Tukey\u2019s\n                    <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                    test or the Kruskal\u2013Wallis test with Dunn\u2019s\n                    <jats:italic toggle=\"yes\">post hoc<\/jats:italic>\n                    test, as appropriate. Inulin increased short-term metabolic activity and partially attenuated 5-FU-induced cytotoxicity, whereas glucomannan demonstrated minimal effects. MCT supplementation further enhanced metabolic activity, indicating differential nutrient\u2013chemotherapy interactions. The combined inulin\u2013MCT\u2013glucomannan formulation exerted the most consistent long-term effects, significantly reducing colony formation and modulating VEGF and IL-6 expression in a dose-dependent manner. However, VEGF increased at higher concentrations. The triple-component formulation modulated proliferative capacity and inflammatory-angiogenic signaling and altered cellular responses to 5-FU, supporting a modulatory rather than uniformly sensitizing role in CRC cells.\n                  <\/jats:p>","DOI":"10.4103\/japtr.japtr_39_26","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:00:21Z","timestamp":1786546821000},"page":"309-315","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Combined inulin, glucomannan, and medium-chain triglyceride modulate metabolic and inflammatory responses in chemotherapy-treated colorectal cancer cells"],"prefix":"10.4103","volume":"17","author":[{"given":"Bernadette Dian","family":"Novita","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapy, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudy","family":"Tjahjono","sequence":"additional","affiliation":[{"name":"Department of Faculty of Pharmacy, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Ervina","sequence":"additional","affiliation":[{"name":"Department of Faculty of Pharmacy, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suryo","family":"Kuncorojakti","sequence":"additional","affiliation":[{"name":"Research Center for Vaccine Technology and Development, Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi Yasmin","family":"Wijaya","sequence":"additional","affiliation":[{"name":"Magister Program Faculty of Medicine Airlangga University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I Gede Putu Adhi","family":"Wedharga","sequence":"additional","affiliation":[{"name":"Department of Undergraduate Program, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendy","family":"Wijaya","sequence":"additional","affiliation":[{"name":"Department of Faculty of Pharmacy, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sianty","family":"Dewi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Herjuniato","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix Christ","family":"Antono","sequence":"additional","affiliation":[{"name":"Department of Undergraduate Program, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Valerie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapy, Faculty of Medicine, Widya Mandala Surabaya Catholic University, Surabaya, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hevi","family":"Wihadmadyatami","sequence":"additional","affiliation":[{"name":"Medical Veterinary Faculty, University of Gadjah Mada, Yogyakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"R1-20260826","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","article-title":"Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from GLOBOCAN","volume":"72","author":"Morgan","year":"2023","journal-title":"Gut"},{"key":"R2-20260826","doi-asserted-by":"crossref","first-page":"101478","DOI":"10.1016\/j.xcrm.2024.101478","article-title":"Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy","volume":"5","author":"Kang","year":"2024","journal-title":"Cell Rep Med"},{"key":"R3-20260826","doi-asserted-by":"crossref","first-page":"851401","DOI":"10.3389\/fphar.2022.851401","article-title":"HIF1a\/VEGF feedback loop contributes to 5-fluorouracil resistance","volume":"13","author":"Shi","year":"2022","journal-title":"Front Pharmacol"},{"key":"R4-20260826","doi-asserted-by":"crossref","first-page":"117793","DOI":"10.1016\/j.bcp.2026.117793","article-title":"5-fluorouracil-induced intestinal mucositis: Pathogenesis and potential therapeutic interventions","volume":"247","author":"Li","year":"2026","journal-title":"Biochem Pharmacol"},{"key":"R5-20260826","doi-asserted-by":"crossref","first-page":"201","DOI":"10.32604\/or.2022.027584","article-title":"Konjac glucomannan enhances 5-FU-induced cytotoxicity of hepatocellular carcinoma cells via TLR4\/PERK\/CHOP signaling to induce endoplasmic reticulum stress","volume":"30","author":"Shi","year":"2022","journal-title":"Oncol Res"},{"key":"R6-20260826","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jff.2024.106367","article-title":"HP inulin-MCT dietary fiber improves lipid metabolism and prevents non-alcoholic steatohepatitis in obese mice","volume":"120","author":"Tjahjono","year":"2024","journal-title":"J Funct Foods"},{"key":"R7-20260826","first-page":"5379","article-title":"Gut fermentation products of inulin-type fructans modulate the expression of xenobiotic-metabolising enzymes in human colonic tumour cells","volume":"32","author":"Munjal","year":"2012","journal-title":"Anticancer Res"},{"key":"R8-20260826","doi-asserted-by":"crossref","first-page":"963","DOI":"10.3390\/nu10080963","article-title":"Medium-chain triglycerides lower blood lipids and body weight in streptozotocin-induced type 2 diabetes rats","volume":"10","author":"Sung","year":"2018","journal-title":"Nutrients"},{"key":"R9-20260826","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.3390\/microorganisms13092068","article-title":"Effects of dietary fiber supplementation on gut microbiota and bowel function in healthy adults: A randomized controlled trial","volume":"13","author":"Inoue","year":"2025","journal-title":"Microorganisms"},{"key":"R10-20260826","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2023.1226448","article-title":"Inulin ameliorates metabolic syndrome in high-fat diet-fed mice by regulating gut microbiota and bile acid excretion","volume":"14","author":"Huang","year":"2023","journal-title":"Front Pharmacol"},{"key":"R11-20260826","doi-asserted-by":"crossref","first-page":"10277","DOI":"10.1021\/jf102127k","article-title":"Comparative effects of cellulose and soluble fibers (pectin, konjac glucomannan, inulin) on fecal water toxicity toward Caco-2 cells, fecal bacteria enzymes, bile acid, and short-chain fatty acids","volume":"58","author":"Chen","year":"2010","journal-title":"J Agric Food Chem"},{"key":"R12-20260826","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.3892\/ol.2020.11790","article-title":"Konjac glucomannan reverses multi-drug resistance of HepG2\/5-FU cells by suppressing AKT signaling and increasing p53 expression","volume":"20","author":"Chen","year":"2020","journal-title":"Oncol Lett"},{"key":"R13-20260826","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1016\/j.ijbiomac.2020.05.105","article-title":"In vivo antioxidant and anti-inflammatory effects of soluble dietary fiber konjac glucomannan in type-2 diabetic rats","volume":"159","author":"Zhao","year":"2020","journal-title":"Int J Biol Macromol"},{"key":"R14-20260826","doi-asserted-by":"crossref","first-page":"102963","DOI":"10.1016\/j.isci.2021.102963","article-title":"Medium-chain triglycerides inhibit long-chain triglyceride-induced GIP secretion through GPR120-dependent inhibition of CCK","volume":"24","author":"Murata","year":"2021","journal-title":"iScience"},{"key":"R15-20260826","doi-asserted-by":"crossref","first-page":"9377","DOI":"10.1021\/acs.jafc.2c02660","article-title":"Medium chain triglycerides promote the uptake of b-carotene in O\/W emulsions via intestinal transporter SR-B1 in Caco-2 cells","volume":"70","author":"Zheng","year":"2022","journal-title":"J Agric Food Chem"},{"key":"R16-20260826","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1186\/s40001-024-02224-5","article-title":"Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease","volume":"29","author":"Wang","year":"2024","journal-title":"Eur J Med Res"},{"key":"R17-20260826","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1038\/s12276-024-01211-4","article-title":"Socialized mitochondria: Mitonuclear crosstalk in stress","volume":"56","author":"Kim","year":"2024","journal-title":"Exp Mol Med"},{"key":"R18-20260826","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1017\/S0007114520004924","article-title":"Effects of dietary fibre intake in chemotherapy-induced mucositis in murine model","volume":"126","author":"Gallotti","year":"2021","journal-title":"Br J Nutr"}],"container-title":["Journal of Advanced Pharmaceutical Technology &amp; Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/JAPTR.JAPTR_39_26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:01:06Z","timestamp":1787745666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/JAPTR.JAPTR_39_26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/japtr.japtr_39_26","relation":{},"ISSN":["2231-4040","0976-2094"],"issn-type":[{"value":"2231-4040","type":"print"},{"value":"0976-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-02-11","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-18","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}