Iron and cancer: recent insights

Abstract

Iron is an essential dietary element. However, the ability of iron to cycle between oxidized and reduced forms also renders it capable of contributing to free radical formation, which can have deleterious effects, including promutagenic effects that can potentiate tumor formation. Dysregulation of iron metabolism can increase cancer risk and promote tumor growth. Cancer cells exhibit an enhanced dependence on iron relative to their normal counterparts, a phenomenon we have termed iron addiction. Work conducted in the past few years has revealed new cellular processes and mechanisms that deepen our understanding of the link between iron and cancer. Control of iron efflux through the combined action of ferroportin, an iron efflux pump, and its regulator hepcidin appears to play an important role in tumorigenesis. Ferroptosis is a form of iron-dependent cell death involving the production of reactive oxygen species. Specific mechanisms involved in ferroptosis, including depletion of glutathione and inhibition of glutathione peroxidase 4, have been uncovered. Ferritinophagy is a newly identified mechanism for degradation of the iron storage protein ferritin. Perturbations of mechanisms that control transcripts encoding proteins that regulate iron have been observed in cancer cells, including differences in miRNA, methylation, and acetylation. These new insights may ultimately provide new therapeutic opportunities for treating cancer.

Estrogen-Dependent Downregulation of Hepcidin Synthesis Induces Intracellular Iron Efflux in Cancer Cells In Vitro

“…The ability of high dose E2 treatment to manipulate iron homeostasis and enhance intracellular iron efflux could provide further insight into the anti-carcinogenic potential of E2 [24,37,39,45]. This is based on the fact that the expression profile hepcidin, FPN, and intracellular iron content in E2-treated MCF-7 cells as documented in this study is the exact opposite of that observed in typical breast cancer cells [24].…”

Novel non-apoptotic cell death: ferroptosis

“…철은 산소 수송과 DNA 생합성 및 ATP 합성에 관여하는 인자로 세포 생존에 매우 중요한 역할을 한다 [2,3]. 철은 체내 포화지방산의 지질 과산화를 유도하며, 미토콘드리아에서 ATP 합성과 함께 활성 산소(reactive oxygen species)를 생성한다 [4].…”

Anticoagulation, ferrotoxicity and the future of translational lung cancer research

“…Aberrant tumor cell iron handling is central to its toxicity (43,44). Studies underway should clarify effects of iron in experimental (45)(46)(47) and human (48)(49)(50) malignancy. Little information is available on effects of iron reduction on blood coagulation.…”