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microbiome is capable of modulating the bioavailability of chemotherapy drugs, mainly due to metabolizing these agents. Multiple cytostatic bacterial metabolites were recently identified that have cytostatic effects on cancer cells. In this study, we addressed the question of whether a set of cytostatic bacterial metabolites (cadaverine, indolepropionic acid and indoxylsulfate) can interfere with the cytostatic effects of the chemotherapy agents used in the management of breast cancer (doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib, 5-fluorouracil and paclitaxel). The chemotherapy drugs were applied in a wide concentration range to which a bacterial metabolite was added in a concentration within its serum reference range, and the effects on cell proliferation were assessed. There was no interference between gemcitabine, irinotecan, methotrexate or rucaparib and the bacterial metabolites. Nevertheless, cadaverine and indolepropionic acid modulated the Hill coefficient of the inhibitory curve of doxorubicin and 5-fluorouracil. Changes to the Hill coefficient implicate alterations to the kinetics of the binding of the chemotherapy agents to their targets. These effects have an unpredictable significance from the clinical or pharmacological perspective. Importantly, indolepropionic acid decreased the IC50 value of paclitaxel, which is a potentially advantageous combination.<\/jats:p>","DOI":"10.3390\/molecules29133073","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T11:19:02Z","timestamp":1719487142000},"page":"3073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cytostatic Bacterial Metabolites Interfere with 5-Fluorouracil, Doxorubicin and Paclitaxel Efficiency in 4T1 Breast Cancer Cells"],"prefix":"10.3390","volume":"29","author":[{"given":"Szandra","family":"Schwarcz","sequence":"first","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Nyerges","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4057-4826","authenticated-orcid":false,"given":"T\u00edmea Ingrid","family":"B\u00edr\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Janka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, MTA Centre of Excellence, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN-UD Allergology Research Group, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-6616","authenticated-orcid":false,"given":"P\u00e9ter","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HUN-REN-UD Cell Biology and Signaling Research Group, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"MTA-DE Lend\u00fclet Laboratory of Cellular Metabolism, 4032 Debrecen, Hungary"},{"name":"Research Center for Molecular Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7584-445X","authenticated-orcid":false,"given":"Edit","family":"Mik\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"MTA-DE Lend\u00fclet Laboratory of Cellular Metabolism, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.ccell.2021.08.006","article-title":"Microbiome and cancer","volume":"39","author":"Cullin","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1007\/s10555-021-10013-3","article-title":"The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer","volume":"40","author":"Ujlaki","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.bbabio.2018.04.002","article-title":"Lithocholic acid, a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness","volume":"1859","author":"Miko","year":"2018","journal-title":"Biochim. 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