{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:15:55Z","timestamp":1772756155439,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T00:00:00Z","timestamp":1678752000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish research council FORMAS","award":["2014\u2013417"],"award-info":[{"award-number":["2014\u2013417"]}]},{"name":"internal university funding","award":["2014\u2013417"],"award-info":[{"award-number":["2014\u2013417"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We previously showed that two iron compounds that are orally ingested by humans, namely ferric EDTA and ferric citrate, can induce an oncogenic growth factor (amphiregulin) in human intestinal epithelial adenocarcinoma cell lines. Here, we further screened these iron compounds, plus four other iron chelates and six iron salts (i.e., 12 oral iron compounds in total), for their effects on biomarkers of cancer and inflammation. Ferric pyrophosphate and ferric EDTA were the main inducers of amphiregulin and its receptor monomer, IGFr1. Moreover, at the maximum iron concentrations investigated (500 \u00b5M), the highest levels of amphiregulin were induced by the six iron chelates, while four of these also increased IGfr1. In addition, we observed that ferric pyrophosphate promoted signaling via the JAK\/STAT pathway by up-regulating the cytokine receptor subunit IFN-\u03b3r1 and IL-6. For pro-inflammatory cyclooxygenase-2 (COX-2), ferric pyrophosphate but not ferric EDTA elevated intracellular levels. This, however, did not drive the other biomarkers based on COX-2 inhibition studies and was probably downstream of IL-6. We conclude that of all oral iron compounds, iron chelates may particularly elevate intracellular amphiregulin. Ferric pyrophosphate additionally induced COX-2, probably because of the high IL-6 induction that was observed with this compound.<\/jats:p>","DOI":"10.3390\/ijms24065507","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:29:16Z","timestamp":1678764556000},"page":"5507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential Effects of Iron Chelates vs. Iron Salts on Induction of Pro-Oncogenic Amphiregulin and Pro-Inflammatory COX-2 in Human Intestinal Adenocarcinoma Cell Lines"],"prefix":"10.3390","volume":"24","author":[{"given":"Agata","family":"Tarczykowska","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Chalmers University of Technology, 412 96 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2399-985X","authenticated-orcid":false,"given":"Niklas","family":"Engstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Chalmers University of Technology, 412 96 Gothenburg, Sweden"},{"name":"Department of Laboratory Medicine, Lund University, 221 00 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darja","family":"Dobermann","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Chalmers University of Technology, 412 96 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8812-9025","authenticated-orcid":false,"given":"Nathalie","family":"Scheers","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Chalmers University of Technology, 412 96 Gothenburg, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1158\/1055-9965.EPI-13-0733","article-title":"Iron and Cancer Risk\u2014A Systematic Review and Meta-analysis of the Epidemiological Evidence","volume":"23","author":"Jakszyn","year":"2014","journal-title":"Cancer Epidemiol. 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