Iron intervenes on several levels in cancer biology. In excess, it can promote cancers. But a new French study recently highlighted a mechanism by which iron could help destroy cancer cells. Explanations.
When the body lacks iron (anemia) or when it has excess, it can have health consequences. Indeed, iron is an essential mineral for the formation of hemoglobin, the protein which transports oxygen in the red blood cells.
The iron deficit is widespread in the population, especially in women and anemia, which is characterized by a deficit of red blood cells in the blood, would affect approximately a quarter of the world’s population.
Is the iron level linked to cancer?
Iron involvement in cancer is complex. This is why the fight against cancer is actively interested in it.
Too much iron and cancer
Epidemiological studies have demonstrated an association between excess iron and the increase in the incidence and risk of cancer (1). The excess food iron seems to be associated with a higher risk of certain cancers, either because iron is the cause of very reactive particles called free radicals, or because it intervenes in other reactions. For example, if you eat a lot of food iron and at the same time swallow a large quantity of nitrates (polluted water), may appear in the body of nitrosamines carcinogens.
An excess of red meat also results in an excess of iron in the body, especially in men and also in women over 50.
As a dividing metal, iron can under certain conditions interact with oxygen in reactions likely to damage DNA, cells and tissues when it is excess.
Iron and colorectal cancer
Hemine iron, present in red meats, is associated with a higher risk of colon adenoma, as shown by a French study on a cohort of more than 17,000 women (2). Epidemiology shows that consumption of red meat and processed meat (cold cuts) is associated with an increased risk of colorectal cancer (3).
Cancer treatment and lack of iron (anemia)
Cancer can promote anemia because chemotherapy treatments slow down the renewal of blood cells. Anemia is therefore frequent in cancer patients.
Iron sources in food
In food, iron is presented in two forms: hemine (in red meat, liver) or non-hemique (in plants). The plants containing iron are for example: seaweed, cocoa, sunflower seeds, wheat sound …
Read: The plants richest in iron
Metastatic cancers: why research is interested in iron
A better understanding of iron metabolism in cancer could allow new therapeutic approaches. One of them is based on activating ferroptosis.
Ferroptosis: What is it?
Ferroptosis is a process of cell death (apoptosis) catalyzed by iron which causes oxidation and degradation of membrane lipids. Ferroptosis is a mechanism that has already been identified as being able to participate in Alzheimer’s disease. According to some work, microglia cells, which are brain immune cells, die because of iron toxicity.
Read: Alzheimer’s: the iron track
Iron toxicity could be used to destroy pro-metastatic cancer cells rich in iron. This is what French researchers have recently demonstrated.
Target iron to fight against metastases: the work of the team of Raphaël Rodriguez
Raphaël Rodriguez’s team depends on the Institut Curie, the CNRS and Inserm. His work has resulted in the design of a new class of molecules capable of inducing the death of persistent cancer cells with high metastatic potential.
Indeed, current anticancer treatments essentially target cells that proliferate quickly, but struggle to eliminate all cancer cells with metastatic potential which are capable of adapting to treatments. These “persistent” cancer cells, with high metastatic potential, express on their surface a large amount of CD44 protein, which allows them to internalize iron, giving them greater aggressiveness and increased capacity to adapt to treatments. These cells are also more sensitive to ferroptosis.
“”Ferroptosis is a vulnerability of the cell to chemistry ironexplains Raphaël Rodriguez, research director at CNRS (4) . In response to a high internal iron concentration, the cell invents mechanisms to neutralize the deleterious effects. For a cancer cell, if the neutralizing mechanisms are always effective, then the cell lives, adapts and can metastate. On the other hand, if the cell is not able to accommodate the side effects of a high iron concentration (in this case, the Production of radicals free of oxygen), well, she dies.»»
Ferroptosis is a vulnerability of the cell to iron chemistry
Hope against breast and pancreas cancers
The researchers developed a molecule that triggers ferroptosis: fentomycin or fento1. After the administration of this molecule, the researchers observed“a significant reduction in tumor growth In preclinical models of breast cancer metastatic as well as a cytotoxic effect pronounced on Biopsies of pancreatic cancer and patient sarcomasconfirming the effectiveness of treatment at the pre-clinical level “explains the Inserm press release (5).
More specifically, in the cell, when the iron is internalized as well as the fanto-1 molecule, they are found in a bag of enzymes called “lysosome”. Under the acid conditions of lysosome, activation of iron chemistry leads to the production of free oxygen radicals, with the consequence of the degradation of membrane lipids.
“” Our goal is clear: it is to tip the scales towards death rather than dissemination. For this, there is a shooting window to exploit this abundance of iron explains Raphaël Rodriguez. Our idea is to saturate cell protection systems, exacerbating the reactivity of iron, in order to initiate the propagation of the alteration of lipids.»»
These results were published in the journalNature(6).
