Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Tarczykowska, Agata ; Engström, Niklas LU ; Dobermann, Darja ; Powell, Jonathan and Scheers, Nathalie (2023) In International Journal of Molecular Sciences 24(6).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amphiregulin, COX-2, ferric pyrophosphate, IFNGR1, IGF1R, IL-6, iron
in
International Journal of Molecular Sciences
volume
24
issue
6
article number
5507
publisher
MDPI AG
external identifiers
  • scopus:85151484406
  • pmid:36982582
ISSN
1661-6596
DOI
10.3390/ijms24065507
language
English
LU publication?
yes
id
ad92bce9-e296-4ef1-9d5d-a92160f732ba
date added to LUP
2023-05-23 11:35:28
date last changed
2024-04-19 22:06:46
@article{ad92bce9-e296-4ef1-9d5d-a92160f732ba,
  abstract     = {{<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 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.</p>}},
  author       = {{Tarczykowska, Agata and Engström, Niklas and Dobermann, Darja and Powell, Jonathan and Scheers, Nathalie}},
  issn         = {{1661-6596}},
  keywords     = {{amphiregulin; COX-2; ferric pyrophosphate; IFNGR1; IGF1R; IL-6; iron}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  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}},
  url          = {{http://dx.doi.org/10.3390/ijms24065507}},
  doi          = {{10.3390/ijms24065507}},
  volume       = {{24}},
  year         = {{2023}},
}