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
Journal article, 2023

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 µM), 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-γr1 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.

IL-6

COX-2

amphiregulin

IGF1R

IFNGR1

ferric pyrophosphate

iron

Author

Agata Tarczykowska

Chalmers, Life Sciences, Food and Nutrition Science

Niklas Engström

Chalmers, Life Sciences, Food and Nutrition Science

Lund University

Darja Dobermann

B administration

Jonathan J. Powell

University of Cambridge

Department of Veterinary Medicine

Nathalie Scheers

Chalmers, Life Sciences, Food and Nutrition Science

International Journal of Molecular Sciences

16616596 (ISSN) 14220067 (eISSN)

Vol. 24 6 5507

Säker berikning av livsmedel: Sambandet mellan järntillskott och colon cancer - Beror det på järnets oxidationstillstånd?

Formas (222-2014-417), 2015-01-01 -- 2019-12-31.

Subject Categories

Immunology in the medical area

Pharmacology and Toxicology

DOI

10.3390/ijms24065507

PubMed

36982582

More information

Latest update

5/3/2023 5