Anti-cancer diet
Low-protein diet activates immune cells capable of killing cancer
Maria Perepechaeva, "First-hand Science"
Which diet is healthier – low-carb or high-fat? Or is it balanced, as logic and common sense tell us? It seems that normally our body is able to cope with any gastronomic experiments, but in case of illness it is better to adhere to the recommendations of specialists. Judging by the results of recent studies, in oncological diseases, preference should be given to food with a low protein content.
A recognized way to increase life expectancy and reduce the risk of developing various diseases, including cancer, is to limit calorie intake. This makes the tumor more sensitive to therapy, including by strengthening the work of the immune system aimed at recognizing and destroying cancer cells. However, cancer patients themselves have a hard time with food restrictions, so scientists are looking for a way to achieve the same effect in other ways. And one of the options is to change the ratio of proteins, fats and carbohydrates without reducing the total caloric content of the diet.
The effect of a low-protein diet on the course of oncological diseases was studied by scientists from Greece and France on laboratory mice with lymphoma, colorectal carcinoma and melanoma (Rubio-Patiño et al., Low-Protein Diet Induces IRE1a-Dependent Anticancer Immunosurveillance, Cell Metabolism, 2018). The animals were divided into 3 groups: one received a feed with a low protein content, the second – carbohydrates, and the third – a balanced feed. At the same time, the total number of calories in the diet was the same.
It turned out that a low-carb diet did not affect the survival of animals, but a diet containing a quarter less protein than usual had an antitumor effect.
As it turned out, this effect was mediated by the activation of immune system cells capable of killing cancer cells.
It is known that a low–protein diet affects the work of the endoplasmic reticulum, an intracellular membrane structure that provides multi-stage synthesis and transport of proteins, as well as the proteostasis system responsible for the correct stacking of protein molecules during their maturation. The endoplasmic reticulum is a dynamic system, the efficiency of which depends on the balance between the amount of biosynthetic load and its "throughput". And if this balance is disturbed, the maturation of proteins will go with errors.
The accumulation of improperly folded proteins causes the so-called stress of the endoplasmic reticulum, as a result of which the cell may die. However, there are mechanisms that suppress protein synthesis and contribute to the destruction of mRNAs that serve as matrices for their assembly, which gives the cell the opportunity to "catch its breath" and "reboot". These regulatory molecular mechanisms share a common trigger of three transmembrane proteins – IRE1a, ATF6a and PERK kinase.
It is known that the chronically occurring adaptive response to stress of the endoplasmic reticulum creates favorable conditions for the development of a tumor, forming a favorable microenvironment for it and contributing to the formation of protection from the body's immune system. However, some forms of endoplasmic reticulum stress can, on the contrary, provoke immunogenic death of cancer cells.
The low-protein diet activated the IRE1a protein in cancer cells and, accordingly, triggered the IRE1a-dependent type of stress response of the endoplasmic reticulum. IRE1a itself, in turn, activated the RIG-I protein involved in the immune response, which served as a trigger for further events.
To test their findings, the scientists injected animals with IRE1a inhibitors, and also removed the IRE1a or RIG-I genes in mouse colorectal carcinoma cells using the CRISPR/Cas9 genome editing method. In all these cases, the positive effect of low-protein food on the survival of sick mice disappeared.
It is still unclear whether the results obtained can be used for cancer patients. However, scientists have already begun relevant studies on human tumor cell lines, and the first data have already confirmed the existence of a link between the activation of the human IRE1a protein and cells of the immune system.
By the way, today experts prescribe a low-protein diet to people suffering from kidney and liver diseases, as well as, for example, with the hereditary disease phenylketonuria, associated with a violation of the metabolism of the amino acid phenylalanine. It is undesirable and even dangerous for a healthy person to use this type of diet.
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