It has long been known that excessive consumption of red meat increases the risk of developing colorectal cancer. As the Technical University (TU) Kaiserslautern writes in a press release, the organic compound “haem iron” is suspected to be responsible for its cancer-promoting effect. A research team at the university has now succeeded in describing the toxic effect of haem-iron in healthy intestinal cells.
Scientific studies have shown that certain factors can increase the risk of colon cancer. These include lack of exercise, overweight, smoking and alcohol consumption. Frequent consumption of red meat also increases the risk of bowel cancer. Researchers have now gained new insights into why this is so.
According to experts, colorectal cancer is one of the three most common types of cancer worldwide. Recently, there has been a continuous increase in the number of new cases, especially among young and middle-aged people between 20 and 50 years. This is mainly associated with changes in dietary habits – including excessive consumption of red meat. The Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI) explains that the frequent consumption of red or processed meat is one of the most important risk factors, along with tobacco consumption, obesity, lack of exercise, a low-fiber diet and frequent alcohol consumption.
Consumption of red meat a risk factor
To understand the role of heme iron in this context, a research team led by Professor Jörg Fahrer from Food Chemistry and Toxicology at the Technical University of Kaiserslautern and the Institute of Toxicology at the University Medical Center Mainz analyzed the effects of the organic iron compound on healthy intestinal cells and degenerated intestinal cancer cells. Furthermore, they investigated the extent to which organic heme iron differs from inorganic forms of iron such as ferric chloride in its potential toxic effects.
The results of the study, which was conducted in cooperation with scientists from the University of Constance and the University of Potsdam and financially supported by the German Research Foundation (DFG), were recently published in the journal “Cell Death & Disease”.
The researchers were initially able to show that haem iron in physiologically relevant concentrations, such as can occur in our intestines, promotes the formation of reactive oxygen species and causes damage to our genetic material, DNA. “These effects were only slightly pronounced in inorganic iron compounds,” explains Dr. Nina Seiwert, first author of the study and post-doctoral fellow in the Drivers working group. Hem-iron, but not the inorganic iron, led to the death of normal intestinal cells, which could also be confirmed in so-called organoids from healthy intestinal tissue.
In the further course the scientists investigated the answer on the cellular level and could show that haem-iron activates a cellular sensor for oxidative stress and thus the enzyme HO-1 is produced in intestinal cells. “HO-1 is responsible for the degradation of heme iron into inorganic iron and other products,” said Professor Fahrer. In order to find out more about the role of HO-1, the researchers used pharmacological and molecular genetic methods. When the production of HO-1 was appropriately deactivated, the concentration of reactive oxygen species rose sharply, leading to increased oxidative DNA damage and ultimately cell death.
“This is virtually a miniorgan that grows in culture dishes embedded in a matrix with a special nutrient medium,” explains Dr. Seiwert. Interestingly, however, the colorectal cancer cells showed a lower sensitivity to heme iron and survived despite the damage.
“Taken together, these findings illustrate that free heme iron has a toxic effect in cells and HO-1 has a very important protective function”, says Professor Fahrer. As the communication concludes, the study thus makes an important contribution to understanding the toxic effect of heme iron in intestinal cells and shows how it can promote the development of intestinal cancer as a component of red meat. (ad)
On the trail of the development of colorectal cancer
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