Repository logo
 

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.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Tarczykowska, Agata 
Dobermann, Darja 
Powell, Jonathan 

Abstract

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.

Description

Keywords

COX-2, IFNGR1, IGF1R, IL-6, amphiregulin, ferric pyrophosphate, iron, Humans, Cyclooxygenase 2, Salts, Edetic Acid, Amphiregulin, Interleukin-6, Janus Kinases, STAT Transcription Factors, Signal Transduction, Iron, Iron Chelating Agents, Ferric Compounds, Iron Compounds, Cell Line, Biomarkers, Adenocarcinoma

Journal Title

Int J Mol Sci

Conference Name

Journal ISSN

1661-6596
1422-0067

Volume Title

24

Publisher

MDPI AG
Sponsorship
Swedish Research Council for Environment Agricultural Sciences and Spatial Planning (2014-417)