Ferric citrate and ferric EDTA but not ferrous sulfate drive amphiregulin-mediated activation of the MAP kinase ERK in gut epithelial cancer cells
Journal article, 2018

Ferric chelates may be used as oral iron supplements or phosphate binders but both ferric citrate and ferric EDTA have been shown to promote tumor burden in murine models of colon cancer. Here we studied their effects on cancer cell growth, at typical supplemental iron levels encountered in the gastrointestinal tract (0.01-0.2 mM). Caco-2 and/or Hutu-80 cells were exposed to these forms of chelated iron or to ferrous sulfate and outcomes were assessed using cell proliferation assays, proteome profiler arrays, western blot, and ELISA. Ferric EDTA and ferric citrate increased cellular levels of the onco-protein amphiregulin and its receptor (EGFr) which in turn stimulated the activation of the MAP kinase ERK. Simultaneously, the expression of the negative Wnt regulator, DKK-1, increased suggesting that cell proliferation through the Wnt pathway may be less pronounced in the presence of ferric EDTA and ferric citrate, unlike for ferrous sulfate. Moreover, ferrous sulfate did not increase levels of cellular amphiregulin or EGFr. We conclude that specific iron compounds affect cell signaling differently and some may increase the risk of colon cancer advancement in an amphiregulin-dependent fashion. Further scrutiny of safe oral iron use is merited.

Ferric EDTA



Ferric citrate



Nathalie Scheers

Chalmers, Biology and Biological Engineering, Food and Nutrition Science

Dora I.A. Pereira

University of Cambridge

Nuno Faria

University of Cambridge

Jonathan J. Powell

University of Cambridge


19492553 (eISSN)

Vol. 9 24 7066-17077

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.

Driving Forces

Sustainable development

Subject Categories

Cell and Molecular Biology


Cancer and Oncology

Areas of Advance

Life Science Engineering (2010-2018)



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