- Researchers investigated the effects of a low-protein diet on the growth of colorectal cancer.
- They found that a low-protein diet reduced tumor growth and increased cancer cell death in mice.
- The researchers say more studies are needed to determine whether the findings can be applied to humans.
Colon cancer occurs when cells in the large intestine or rectum get out of control. The National Cancer Institute of the United States estimates that the disease accounted for 7.9% of new cancer cases in the US and 8.6% of cancer deaths in 2022.
Studies show that nutrient-sensing molecules, known as mTORC1, contribute to tumor growth and are hyperactivated in approximately 70% of human cancers, including colorectal cancer. Animal studies show that mTORC1 inhibition inhibits tumor growth.
Although drugs that inhibit the mTORC1 pathway have been shown to be clinically effective, their use is limited as tumors often recur after discontinuation of treatment and side effects include immunosuppression.
Studies show that amino acids activate mTORC1, and restricting dietary protein may inhibit tumor growth by reducing mTORC1.
Further research on how restricting dietary proteins affects mTORC and tumor growth could improve cancer treatment.
Recently, researchers investigated the effects of low-protein diets on mTORC1 activation in animal and human tissue models.
“We’ve observed that feeding human colorectal cancer cells with low amino acids and treating them with chemotherapy creates synergies to kill cancer cells,” Dr. Sumeet Solanki, a researcher in molecular and integrative physiology at the University of Michigan, first author of the study, told Medical News Today.
The study was published in Gastroenterology.
Limiting proteins to inhibit tumors
The researchers first examined colorectal cancer cells in mice. They found that mTORC1 activation was higher in the presence of amino acids.
The researchers next looked at how these results were translated into live mice. To do this, they spent two weeks studying the effects of a low-protein diet on mouse models of colorectal cancer, followed by one month of chemotherapy. While mice normally consist of 21% protein, they fed mice with just 4% protein.
They found that mice on a low-protein diet had less early tumour growth and more cancer cell death than control animals. These mice also had reduced mTORC1 activation and proliferation.
The researchers found that this indicates that amino acids regulate mTORC1 activity and that limiting amino acids may inhibit early tumor growth.
Using in vitro tests, the researchers next found that a low-protein diet — and in particular a reduction in the amino acids leucine and cystine — altered nutritional signals to mTORC1 via GATOR1 and GATOR2 protein complexes.
When amino acids are abundant, GATOR2 activates mTORC1. However, when amino acids are low, GATOR1 deactivates mTORC1.
Only some patients could benefit from screening for bowel cancer biopsies in humans
. The researchers also found that more genetic markers for mTORC1 correlated with resistance to chemotherapy and poorer outcomes.
The researchers therefore suggested that screening for genes to recognize amino acids could provide information about which patients would benefit from a low-protein diet and which would not.
Dr. Gretel Terrero, a triple board certified hematologist and medical oncologist at the Miami Cancer Institute, part of Baptist Health South Florida, who was not involved in the study, told Medical News Today:
“[This study implies] that intestinal tumor cells can change the way amino acids are perceived to further activate mTORC1, leading to increased cell growth and proliferation of tumor cells. […] Hyperactive mTORC1 could be exploited by restricting the uptake of amino acids through dietary protein restriction, thus triggering the tumour cell stress and cell death.”
“[The] results also suggest that changes in amino acid sensing pathways may increase resistance to chemotherapy drugs. [Therefore] dietary protein restriction could potentially reduce drug resistance to standard chemotherapy for colorectal cancer.”
— Dr. Gretel Terrero
However, she added that more research is needed to understand the precise molecular signaling pathways that drive tumor growth and resistance.
What nourishes cancer cells
When asked what “feeds” cancer cells, Dr. Solanki found that cancer cells need large amounts of nutrients, including glucose, amino acids, and nucleotides, to reproduce. While some of these nutrients can be synthesized in cells, others, such as amino acids, must be absorbed from food sources.
He continued that sensor pathways such as GATOR and mTORC1 detect nutrient levels and signal cellular mechanisms for division, growth, and proliferation.
“Because the body’s nutrients are affected by diet, we found that feeding animals on a low-protein diet led to a demand and supply crisis for colorectal cancer cells, which resulted in massive cancer cell deaths,” he said.
“Therefore, these types of cancer are metabolically susceptible, and a low-protein diet along with chemotherapy can kill cancer cells in these environments because their demand is high and the supply is low,” he noted.
“Dieting or starving cancer cells is clearly complicated, but this research shows that deficiencies in certain amino acids affect mTORC-1 pathways that lead to cell death.”
When asked about the study’s limitations, Dr. Nelson pointed out that the research was done on mice and cancer cell lines and said it was still “unclear how this could be used clinically in humans.”
Dr. Terrero added that clinical trials remain difficult due to difficulties with patient compliance and control of lifestyle variables that could affect the tumor microenvironment.
Dr. Solanki, meanwhile, said that while the study results are promising, a low-protein diet is not a long-term solution.
The caveats of a low-protein diet for cancer patients
“Since cancer patients often experience muscle atrophy, it is not ideal to provide patients with low protein levels in the long term. Because cancer cells divide quickly, they may need more nutrients to recover after chemotherapy. Therefore, a low-protein diet on important time frames, such as one week before/after chemotherapy, can offer synergies in eradicating these tumour cells with high demand.”
— Dr. Sumeet Solanki
He added that his team is currently investigating whether reducing certain amino acids could mimic the effects of a low-protein diet without negative side effects, such as malnutrition and weight loss.
When asked what these findings might mean for cancer treatment, Dr. Solanki said:
“Extrapolating our results to humans in animal models would be premature, although this is a small step in the right direction. We highly recommend seeking medical advice from an oncologist and nutritionist.”