{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T06:18:39Z","timestamp":1770272319223,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the S\u00e3o Paulo Research Foundation\u2014FAPESP","award":["2021\/09381-3"],"award-info":[{"award-number":["2021\/09381-3"]}]},{"name":"the S\u00e3o Paulo Research Foundation\u2014FAPESP","award":["2022\/13151-6"],"award-info":[{"award-number":["2022\/13151-6"]}]},{"name":"the S\u00e3o Paulo Research Foundation\u2014FAPESP","award":["304333\/2023-9"],"award-info":[{"award-number":["304333\/2023-9"]}]},{"name":"the Coordination for the Improvement of Higher Education Personnel\u2014CAPES","award":["2021\/09381-3"],"award-info":[{"award-number":["2021\/09381-3"]}]},{"name":"the Coordination for the Improvement of Higher Education Personnel\u2014CAPES","award":["2022\/13151-6"],"award-info":[{"award-number":["2022\/13151-6"]}]},{"name":"the Coordination for the Improvement of Higher Education Personnel\u2014CAPES","award":["304333\/2023-9"],"award-info":[{"award-number":["304333\/2023-9"]}]},{"name":"FAPESP scholarship","award":["2021\/09381-3"],"award-info":[{"award-number":["2021\/09381-3"]}]},{"name":"FAPESP scholarship","award":["2022\/13151-6"],"award-info":[{"award-number":["2022\/13151-6"]}]},{"name":"FAPESP scholarship","award":["304333\/2023-9"],"award-info":[{"award-number":["304333\/2023-9"]}]},{"name":"the National Council for Scientific and Technological Development\u2014CNPq","award":["2021\/09381-3"],"award-info":[{"award-number":["2021\/09381-3"]}]},{"name":"the National Council for Scientific and Technological Development\u2014CNPq","award":["2022\/13151-6"],"award-info":[{"award-number":["2022\/13151-6"]}]},{"name":"the National Council for Scientific and Technological Development\u2014CNPq","award":["304333\/2023-9"],"award-info":[{"award-number":["304333\/2023-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Colorectal cancer (CRC) is among the most prevalent malignant neoplasms globally. Chemotherapeutic treatment strategies have demonstrated minimal improvement over the past decade. Combination therapies, including those with nutraceuticals, are currently being investigated as promising alternatives to enhance therapeutic efficacy. The organosulfur garlic extract diallyl disulfide (DADS) has demonstrated anti-tumoral activity in several types of cancer. This study aimed to investigate the effects of DADS and 5-fluorouracil (5-FU), both individually and in combination, on the human CRC cell lines Caco-2 and HT-29. Methods: Caco-2, HT-29, and non-tumoral human umbilical vein endothelial cells (HUVEC) were exposed to DADS (25\u2013600 \u00b5M) and 5-FU (5\u2013100 \u00b5M), either individually or in simultaneous combination (DADS 100 \u00b5M + 5-FU 100 \u00b5M), for 24 h. Cytotoxicity was evaluated in all three cell lines. In addition, the effects of these treatments on oxidative stress, cell migration, genotoxicity, cell death, global DNA methylation, and gene\u2013nutraceutical interactions were assessed in both tumor cell lines. Results: DADS demonstrated cytotoxic effects at high concentrations in Caco-2, HT-29, and HUVECs and induced DNA damage in both colorectal cancer cell lines. The combination of DADS and 5-FU significantly promoted apoptotic cell death, increased genotoxicity, elevated global DNA methylation, and inhibited cell migration, with these effects being particularly pronounced in HT-29 cells. Conclusions: We provide evidence that DADS combined with 5-FU is potentially useful in the therapy of CRC. However the combination of nutraceuticals and chemotherapy must consider the distinct molecular and phenotypic characteristics of each tumor cell line.<\/jats:p>","DOI":"10.3390\/nu17152412","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T10:28:09Z","timestamp":1753352889000},"page":"2412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Toxigenomic Evaluation of Diallyl Disulfide Effects and Its Association with the Chemotherapeutic Agent 5-Fluorouracil in Colorectal Cancer Cell Lines"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8599-4934","authenticated-orcid":false,"given":"Estefani Maria","family":"Treviso","sequence":"first","affiliation":[{"name":"Department of Clinical Analysis, Toxicology Food Science, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline Andolfato","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology Food Science, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cec\u00edlia Cristina Souza","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology Food Science, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0759-4011","authenticated-orcid":false,"given":"Alexandre Ferro","family":"Aissa","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04021-001, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-4388","authenticated-orcid":false,"given":"Lus\u00e2nia Maria Greggi","family":"Antunes","sequence":"additional","affiliation":[{"name":"Department of Clinical Analysis, Toxicology Food Science, School of Pharmaceutical Sciences of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Ribeir\u00e3o Preto 14040-903, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1007\/s11684-024-1058-6","article-title":"Disparities in 36 Cancers across 185 Countries: Secondary Analysis of Global Cancer Statistics","volume":"18","author":"Li","year":"2024","journal-title":"Front. 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