Research reveals new diet to 'self-destruct' brain tumor cells

Cell death is part of the normal functioning of our human body. This natural process is known as apoptosis. However, our bodies block this natural process in cancer cells, making it difficult to remove unwanted cells, which multiply to pose serious health risks.

This is where ferroptosis enters the picture in cancer treatment. “The recent discovery of ferroptosis adds to the excitement of it all. It is really a rapidly growing body of research, and we are finding that it’s a very important for a lot of biological processes, and not just in cancers,” said Dominique Higgins, MD, PhD, an assistant professor in the Department of Neurosurgery at UNC. 

To achieve ferroptosis, scientists remove specific types of amino acids from the patient's diet. This, in turn, allows tumor cells to die. 

The two identified amino acids that can prevent tumors are cysteine and methionine, as per the study. Our bodies obtain these amino acids from our diet. 

“First, we found that when we take away certain amino acids in animal models that the glioblastoma cells are more likely to die by ferroptosis. Secondly, we found that removing these amino acids makes our drugs a lot more effective at inducing ferroptosis in cancer cells,” said Higgins in a statement.

For this study, the team created a customized diet for the animal models by removing cysteine and methionine. The findings demonstrated that glioblastoma cells could die via ferroptosis. The researchers also discovered that after the diet, the cells required lower doses of chemotherapy drugs.

Following this study, the team intends to put this diet method to the test on patients prior to surgery. The authors will be able to learn more about how ferroptosis affect the human body and the tumor as a result of this trial. After the surgery, the team will be able to assess how well the tumors responded to the diet. 

Furthermore, the authors believe that this treatment could be beneficial in the treatment of sarcoma, lung cancer, and pancreatic cancer.

The findings have been published in Nature Communications.

Study Abstract:

Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures. We also show that a cysteine-depleted, methionine-restricted diet can improve therapeutic response to RSL3 and prolong survival in a syngeneic orthotopic murine glioma model. Finally, this CMD diet leads to profound in vivo metabolomic, proteomic and lipidomic alterations, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification