Ethyl Maltol Disrupts Iron Homeostasis in SH-SY5Y Neuroblastoma Cell Line

Ethyl Maltol (EM) is a commonly used flavoring compound and has been reported to bind iron and facilitate iron transport. Because EM is highly lipophilic, the potential that it disrupts intracellular iron homeostasis was investigated. EM increased the labile iron pool in SH-SY5Y cells and increased iron-responsive protein activity using a reporter assay in the HEK293 cells. EM induced the expression of transferrin receptor 1 mRNA and decreased expression of ferritin light chain protein in SH-SY5Y cells. Expression of the iron-responsive protein amyloid precursor protein attenuated the effects of EM on these iron-responsive genes. EM treatment decreased cell viability and increased DNA damage. EM also induced the phosphorylation of p53 and the expression of the p53 regulated genes, p21 and 14-3-3{sigma}. The expression of APP attenuated the effects of EM on viability, DNA damage, and the p53 response. Overall, we suggest that EM decreases cell viability through a mechanism involving the p53 pathway. The attenuated responses observed in cells expressing APP suggests that the effects of EM are due to disrupting iron homeostasis.