{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T18:00:17Z","timestamp":1769536817265,"version":"3.49.0"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana Ricerca sul Cancro","doi-asserted-by":"crossref","award":["IG 2019\u2014ID. 23006"],"award-info":[{"award-number":["IG 2019\u2014ID. 23006"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UIDB\/04050\/2020"],"award-info":[{"award-number":["UIDB\/04050\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre of Molecular and Environmental Biology","award":["UID\/04050"],"award-info":[{"award-number":["UID\/04050"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Pancreatic cancer (PC) and colorectal cancer (CRC) are among the most lethal malignancies, with growing evidence pointing to the gut microbiota\u2019s role in their progression. This study aimed to explore the anticancer potential of two microbiota-derived postbiotics, N-acetylcysteine (NAC) and tetrahydro \u03b2-carboline carboxylic acid (THC), in targeting some hallmark traits of PC and CRC, both as standalone agents and in combination with standard chemotherapeutics (gemcitabine for PC and 5-fluorouracil (5-FU) for CRC). Methods: Cell viability assays and IC50 determination was assessed using either the Muse\u2122 Count &amp; Viability Kit or the Sulforhodamine B assay; cell death was determined by Annexin V\/Propidium Iodide and cell cycle assessed by Propidium Iodide was analyzed by flow cytometry. Results: Here, we found that NAC selectively reduced the viability of PC cells BxPC-3 without triggering apoptosis, while effectively inducing apoptosis in PC cells Panc-1 and in CRC cell lines. THC exhibited stronger anticancer activity, inhibiting proliferation and promoting apoptosis in all tested PC and CRC cells, even at lower concentrations. Combination treatments yielded promising enhancement effects. NAC enhanced the cytotoxicity of gemcitabine in Panc-1 cells through increased apoptosis. NAC, when combined with 5-FU, also increased apoptosis of CRC cells. THC further potentiated gemcitabine\u2019s impact on Panc-1 cells by increasing apoptosis and by inducing cell cycle changes in BxPC-3. In the CRC model, THC co-treatment with 5-FU reduced cell viability and increased apoptosis in all cells. Conclusions: These findings provide preliminary in vitro evidence supporting the potential of integrating microbiota-derived postbiotics with conventional chemotherapy both in PC and CRC.<\/jats:p>","DOI":"10.3390\/cancers18030369","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T11:14:07Z","timestamp":1769426047000},"page":"369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing Postbiotics to Boost Chemotherapy: N-Acetylcysteine and Tetrahydro \u03b2-Carboline Carboxylic Acid as Potentiators in Pancreatic and Colorectal Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Vanessa","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"IBS\u2014Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-8306","authenticated-orcid":false,"given":"Annacandida","family":"Villani","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}]},{"given":"Margarida","family":"S\u00e9nica","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"IBS\u2014Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]},{"given":"Concetta","family":"Panebianco","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-1153","authenticated-orcid":false,"given":"Valerio","family":"Pazienza","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7302-0630","authenticated-orcid":false,"given":"Ana","family":"Preto","sequence":"additional","affiliation":[{"name":"Centre of Molecular and Environmental Biology (CBMA), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"},{"name":"IBS\u2014Institute of Science and Innovation for Bio-Sustainability, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"176013","DOI":"10.1016\/j.ejphar.2023.176013","article-title":"Cancer chemotherapy resistance: Mechanisms and recent breakthrough in targeted drug delivery","volume":"958","author":"Davodabadi","year":"2023","journal-title":"Eur. 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