Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.

Elemental iron has crucial functions in mammalian cells. Iron enables the function of vital iron- and haem-containing enzymes, including mitochondrial enzymes that are involved in respiratory complexes, enzymes involved in DNA synthesis and the cell cycle, detoxifying enzymes such as peroxidase and catalase, and many more1. Therefore, iron is essential for cell replication, metabolism and growth. However, the ability to gain and lose electrons — the very attribute that makes iron useful enzymatically — also enables iron to participate in potentially deleterious free radical-generating reactions. Among these is the Fenton reaction, in which ferrous iron donates an electron in a reaction with hydrogen peroxide to produce the hydroxyl radical, a reactive oxygen species (ROS). This reaction not only damages lipids and proteins, but also causes oxidative damage to DNA, including DNA base modifications and DNA strand breaks2,3, which can be mutagenic4. Therefore, iron is both essential and potentially toxic.

Both the beneficial and deleterious effects of iron have a role in cancer. For example, iron may accelerate tumour initiation by enhancing the formation of free radicals, as well as function as a nutrient that fosters tumour cell proliferation. The extent to which and the mechanisms by which iron has such roles have been debated for decades. As early as 1940, exposure to iron oxide dust was shown to triple the incidence of pulmonary tumours in mice5; in the 1950s, intramuscular injection of iron–dextran was shown to induce sarcoma in rats6. In the 1990s, it was demonstrated that the growth rate of tumour xenografts could be influenced by levels of dietary iron7,8. Many years and experiments later, a clearer picture linking excess iron and altered iron metabolism to cancer is emerging, based on evidence ranging from epidemiological to molecular (TABLE 1).

Article Iron and Cancer: More Ore To Be Mined

Iron is an essential nutrient that facilitates cell proliferation and growth. However, iron also has the capacity to engage in redox cycling and free radical formation. Therefore, iron can contribute to both tumour initiation and tumour growth; recent work has also shown that iron has a role in the tumour microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumour cell survival. Signalling through hypoxia-inducible factor (HIF) and WNT pathways may contribute to altered iron metabolism in cancer. Targeting iron metabolic pathways may provide new tools for cancer prognosis and therapy.

Elemental iron has crucial functions in mammalian cells. Iron enables the function of vital iron- and haem-containing enzymes, including mitochondrial enzymes that are involved in respiratory complexes, enzymes involved in DNA synthesis and the cell cycle, detoxifying enzymes such as peroxidase and catalase, and many more1. Therefore, iron is essential for cell replication, metabolism and growth. However, the ability to gain and lose electrons — the very attribute that makes iron useful enzymatically — also enables iron to participate in potentially deleterious free radical-generating reactions. Among these is the Fenton reaction, in which ferrous iron donates an electron in a reaction with hydrogen peroxide to produce the hydroxyl radical, a reactive oxygen species (ROS). This reaction not only damages lipids and proteins, but also causes oxidative damage to DNA, including DNA base modifications and DNA strand breaks2,3, which can be mutagenic4. Therefore, iron is both essential and potentially toxic.

Both the beneficial and deleterious effects of iron have a role in cancer. For example, iron may accelerate tumour initiation by enhancing the formation of free radicals, as well as function as a nutrient that fosters tumour cell proliferation. The extent to which and the mechanisms by which iron has such roles have been debated for decades. As early as 1940, exposure to iron oxide dust was shown to triple the incidence of pulmonary tumours in mice5; in the 1950s, intramuscular injection of iron–dextran was shown to induce sarcoma in rats6. In the 1990s, it was demonstrated that the growth rate of tumour xenografts could be influenced by levels of dietary iron7,8. Many years and experiments later, a clearer picture linking excess iron and altered iron metabolism to cancer is emerging, based on evidence ranging from epidemiological to molecular (TABLE 1).

Article Iron and Cancer: More Ore To Be Mined

Thank you for the theoretical background of the iron metabolism.

Actually, my question is more technical. Does the amount of iron in the 'iron pool' in cancer cells in vitro aka cultured under common tissue culture conditions [ rcommended and commercially available culture media + FBS, no added Fe-ions i.e. in form of salts or bound otherwise] reflect the amount of iron in cancer cells in vivo [say a human]? I thought it would, more or less. But I am not sure anymore. Where would it come from if it is not supplemented in the media/FBS? To keep it simple: In an organism, say human, the iron comes from the diet, if the intake of iron is low it will be recruited from storage [if I am not mistaken]. Where does a cell in culture gets the iron if not from the media?

Is it necessary to add extra iron to simulate physiological conditions? And if so, how much approximatly [in molars]?

Interesting.

the iron is the essential factor for grow, metabolism and develop even metastasis of cancer cells as well as the most existence element in cancer cells.