Less intake of these two amino acids can accelerate tumor death

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Less intake of these two amino acids can accelerate tumor death

Studies have confirmed that less intake of these two amino acids can accelerate tumor death.

Glioblastoma is the most common type of brain tumor in adults and is extremely aggressive, with a median survival of only about 16 months. However, the scientific community still has no cure for this tumor.

In pursuit of a way to beat glioblastoma, a research team from Columbia University discovered that glioblastoma appears to be highly sensitive to ferroptosis , an iron-dependent programmed cell death that Under the action of ions and ester oxygenase, the unsaturated fatty acids on the cell membrane will undergo lipid peroxidation, resulting in cell death.

Less intake of these two amino acids can accelerate tumor death ▲Related papers have been published in “Nature-Communications”

Like other programmed cell deaths, ferroptosis is tightly controlled to ensure normal cell function. The GPX4 enzyme is responsible for clearing membrane lipid peroxides and preventing cellular dysfunction. GPX4 is often concomitantly inactivated during ferroptosis.

Of course, the GPX4 enzyme also needs glutathione as a cofactor to do its job . This gave the researchers a new idea that glutathione can be generated from cysteine depending on specific biochemical processes, in addition, methionine can also be converted to cysteine regeneration as a supplementary pathway glutathione.

Therefore, these two amino acids have also become the key molecules to control ferroptosis, and they usually need to be ingested through food, which allows researchers to well control the intake of individuals.

In mouse and human glioma cell cultures, when the two amino acids were specifically removed from the culture medium (CMD conditions/diet), the level of tumor cell ferroptosis was rapidly increased , and it also interacted with the GPX4 inhibitor Play a synergistic effect to further increase the sensitivity of glioma cells to ferroptosis.

Less intake of these two amino acids can accelerate tumor death ▲Reducing cysteine and methionine can increase the ferroptosis process of glioma cells (picture source: reference [1])

However, human astrocytes were not sensitive to cell death induced by GPX4 inhibitors and CMD conditions, suggesting that this ferroptosis mechanism may be tumor-specific .

According to the analysis, the metabolism of glioma cells under CMD conditions changed, and the glutathione level was significantly reduced after 48 hours, while the basic respiratory response and mitochondrial metabolism of the cells were also weakened.

In addition, the authors also constructed a batch of mouse model experiments. They tried to inject some glioma cells into the mice.

After a week, the mice were divided into groups according to the conventional diet and the CMD diet. During the entire observation period of the experiment, the mice could tolerate the CMD diet, but their body weight was slightly lower than that of healthy mice.

Less intake of these two amino acids can accelerate tumor death ▲The CMD diet can increase the survival rate of tumor mice (picture source: reference [1])

In terms of survival rate, the CMD diet mice were significantly higher than the normal diet group.

This diet mode can also be used in combination with GPX4 enzyme inhibitors, which can further trigger the ferroptosis process of mouse tumors and further improve the survival rate.

The researchers believe that by eliminating specific components of the diet, it could be a therapeutic option for cancer patients so that patients can still get their other daily nutritional and energy needs .

The research team is planning a clinical trial involving glioblastoma patients by starting them on a CMD diet prior to tumor removal surgery.

In addition to glioblastoma, some studies have also suggested that CMD is also effective in lung and pancreatic cancer models, and may become a more general anti-cancer adjuvant method.

References:
[1] Pavan S. UPADHYAYULA ET Al, Dietary RestricTion of Cyteine and MetHionine Sensitizes Gliomas to Ferroptosis and Induces Alfa SM, Nature Communications (2023). Doi: 10.1038/S41467-023-36630-W
[2] Researchers leverage cell self-destruction to treat brain tumors. Retrieved April 18, 2023 from https://medicalxpress.com/news/2023-04-leverage-cell-self-destruction-brain-tumors.html

Less intake of these two amino acids can accelerate tumor death

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