{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:04:36Z","timestamp":1785524676775,"version":"3.56.0"},"reference-count":44,"publisher":"Wiley","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Colorectal cancer is the third most commonly diagnosed cancer worldwide and the second most common cause of cancer\u2010related death in both men and women. Although a number of treatments are available to combat this malignancy, the antimetabolite 5\u2010fluorouracil has been the cornerstone of therapy since its synthesis in the 1950s. Unfortunately, the prolonged use of 5\u2010fluorouracil can lead to chemoresistance, which has prompted research into combination regimens to improve efficacy and quality of life and reduce resistance. Here, we evaluated the synergistic potential of two compounds isolated from guayule, and argentatins A and B, alone and in combination with 5\u2010fluorouracil in a panel of colorectal cancer cell lines. Cell viability assays showed that the combination treatment (argentatin A with 5 fluorouracil) significantly enhanced cytotoxicity, especially in RKO, where the analysis using the Bliss independence model indicated a remarkable synergistic effect with the lowest doses of both compounds. In contrast to the combination with argentatin B, in which the additive effect was only found in the HCT\u2010116 cell line. Finally, immunocytometric analysis revealed that combination treatments induced higher rates of apoptosis than single\u2010agent treatments. Collectively, our findings indicate that argentatins A and B may enhance the anti\u2010tumour effects of 5\u2010fluorouracil and may represent a promising strategy to improve the efficacy of anticancer therapies based on this antimetabolite.<\/jats:p>","DOI":"10.1111\/jcmm.70294","type":"journal-article","created":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T06:41:17Z","timestamp":1734763277000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic Potential of Argentatins A and B to Improve 5\u2010Fluorouracil Cytotoxicity in Colorectal Cancer Cell Models"],"prefix":"10.1111","volume":"28","author":[{"given":"Paula","family":"S\u00e1nchez\u2010Olivares","sequence":"first","affiliation":[{"name":"Cancer Pathophysiology and Therapy Lab Institute of Biomedicine (IB\u2010UCLM) Universidad de Castilla\u2010La Mancha  Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-7551","authenticated-orcid":false,"given":"Aniela M.","family":"Silva\u2010Nolasco","sequence":"additional","affiliation":[{"name":"Institute for Regional Development (IDR) Universidad de Castilla\u2010La Mancha  Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"de la Cruz\u2010Morcillo","sequence":"additional","affiliation":[{"name":"Institute for Regional Development (IDR) Universidad de Castilla\u2010La Mancha  Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8502-8560","authenticated-orcid":false,"given":"Mar\u00eda Mercedes","family":"Garc\u00eda\u2010Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Universidad de Castilla\u2010La Mancha, E.T.S.I. Agron\u00f3mica, de Montes y Biotecnolog\u00eda (ETSIAMB)  Albacete Spain"},{"name":"Instituto T\u00e9cnico Agron\u00f3mico Provincial de Albacete, ITAP  Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Pinedo\u2010Serrano","sequence":"additional","affiliation":[{"name":"Cancer Pathophysiology and Therapy Lab Institute of Biomedicine (IB\u2010UCLM) Universidad de Castilla\u2010La Mancha  Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8697-8709","authenticated-orcid":false,"given":"Manuel","family":"Carmona","sequence":"additional","affiliation":[{"name":"Institute for Regional Development (IDR) Universidad de Castilla\u2010La Mancha  Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M.","family":"Gal\u00e1n\u2010Moya","sequence":"additional","affiliation":[{"name":"Cancer Pathophysiology and Therapy Lab Institute of Biomedicine (IB\u2010UCLM) Universidad de Castilla\u2010La Mancha  Albacete Spain"},{"name":"Facultad de Enfermer\u00eda Universidad de Castilla\u2010La Mancha  Albacete Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Globocan 2022: Cancer Fact Sheets\u2014Colorectal Cancer","author":"International Agency for Research on Cancer"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0189-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.02.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.321"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v24.i34.3834"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.658636"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165920"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-017-1353-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/agronomy9120804"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.indcrop.2023.117126"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.indcrop.2022.115463"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0304713"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.10.028"},{"key":"e_1_2_10_16_1","article-title":"Isolation and Chemical Transformations of Some Anti\u2010inflammatory Triterpenes from Salvia mexicana L. var. minor Benth","volume":"47","author":"Delira R. 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