The effect of zinc sulfate supplementation on the growth factor Amphiregulin in the human adenocarcinoma cell line Caco-2
Typ
Examensarbete för masterexamen
Program
Publicerad
2022
Författare
Åströms, Marianne
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
Iron deficiency and iron deficiency anemia is a worldwide health problem. In 2016 one billion
people worldwide suffered from iron deficient anemia. To treat or prevent iron deficiency,
iron can be added to the diet as supplements or directly to food. One additive approved by the
European Food Safety Authority for use in foods is ferric EDTA. Unfortunately, ferric EDTA
has been observed to induce the cancer marker Amphiregulin in human cell studies and
increase tumor burden in mice studies. Ferrous sulfate did not affect amphiregulin induction
in human cell studies suggesting that the effect is connected to the affinity of iron to its ligand
and therefore also the binding of iron to its transport protein at the site of absorption in
intestinal cells.
Zinc salts have been observed to interfere with iron uptake by its transporter DMT1 in
intestinal cells. We therefore sought to investigate if zinc sulfate could affect the induction of
amphiregulin in the presence of ferric EDTA. The human intestinal Caco-2 cell model,
validated for iron absorption studies, were incubated with three different iron compounds
(500µM); ferric chloride, ferric EDTA and ferrous fumarate alone and together with zinc
sulfate (20 and 100µM). The cell lysates were then analyzed to predict cell survival and
amphiregulin production.
All treatments induced amphiregulin compared to control; ferric EDTA (316% ±74%), ferric
EDTA + zinc sulfate 100µM (252% ±50%), ferric chloride (157% ±43%), ferric chloride +
zinc sulfate 100µM (157% ±43%), zinc sulfate 100µM (143% ±19%), ferrous fumarate
(120% ±8%), ferrous fumarate + zinc sulfate 100µM (120% ±15%). In this study ferric
EDTA increased amphiregulin levels 3.8-10.8-fold compared to the other treatments but there
was no effect of zinc sulfate (20µM and 100µM) on amphiregulin levels in the presence of
ferric EDTA, ferric chloride or ferrous fumarate at 500µM. Ferric chloride (500µM) was the
only treatment showing a lower cell survival compared to control, ferric chloride (82%
±10%). In conclusion, zinc sulfate at the given concentrations did not lower amphiregulin
induction in the presence of ferric EDTA at 500µM
Beskrivning
Ämne/nyckelord
Zinc sulfate , Amphiregulin , Dietary supplements , Caco-2 cells , Ferric EDTA