- Researchers studied the effects of a low protein diet on colon cancer growth.
- They found that a low protein diet reduces tumor growth and increases cancer cell death in mice.
- The researchers say that further study is needed to see if the results translate to humans.
Colon cancer occurs when cells in the colon or rectum grow out of control. The United States National Cancer Institute estimates that the condition accounted for 7.9% of new cancer cases in the U.S. in 2022, and 8.6% of cancer deaths.
Studies show that nutrient-sensing molecules known as mTORC1 contribute to tumor growth and are hyperactivated in around more than 70% of human cancers, including colon cancer. Animal studies demonstrate that inhibiting mTORC1 inhibits tumor growth.
Although drugs that inhibit the signaling pathway for mTORC1 have been proven to be clinically effective, they are limited in use as tumors often return after treatment ends, and side effects include immunosuppression.
Studies show that amino acids activate mTORC1, and dietary protein restriction may inhibit tumor growth by reducing mTORC1.
Further research into how restricting dietary protein affects mTORC and tumor growth could improve cancer treatments.
Recently, researchers investigated the effects of low protein diets on mTORC1 activation in animal and human tissue models.
“We observed that feeding human-derived colon cancer cells with low amino acids and treating them with chemotherapies synergizes to kill cancer cells,” Dr. Sumeet Solanki, research investigator 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 protein to inhibit tumors
The researchers first assessed colon cancer cells in mice. They found that mTORC1 activation was higher in the presence of amino acids.
The researchers next investigated how these findings translated into live mice. To do so, they assessed the effects of a low protein diet on mouse models of colon cancer for two weeks, followed by a month of chemotherapy. Whereas mouse diets are typically 21% protein, they fed mice diets with just 4% protein.
They found that mice on a low protein diet displayed less early tumor growth and more cancer cell death than controls. These mice also had reduced mTORC1 activation and proliferation.
The researchers noted that this suggests that amino acids regulate mTORC1 activity and that limiting amino acids may inhibit early tumor growth.
From in-vitro tests, the researchers next found that a low protein diet—and specifically reduction of 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 may see benefit
From testing human colon cancer biopsies, the researchers also found that more genetic markers of mTORC1 correlated with resistance to chemotherapy and worse outcomes.
The researchers thus suggested that screening for amino acid sensing genes could inform 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 Miami Cancer Institute, part of Baptist Health South Florida, who was not involved in the study, told Medical News Today:
“[This study implies] that colon tumor cells may change the way amino acids are sensed to further activate mTORC1, leading to increased cell growth and proliferation of tumor cells. […] Hyperactive mTORC1 could be taken advantage of by restricting intake of amino acids- via dietary protein restriction- and thus triggering tumor cell stress and death.”
“[The] results also suggest that changes in amino acid sensing pathways may drive chemotherapy drug resistance. [Therefore], dietary protein restriction could potentially decrease drug resistance to standard chemotherapy in colorectal cancer.”
— Dr. Gretel Terrero
She added, however, that further research is needed to understand the exact molecular pathways that drive tumor growth and resistance.
What feeds cancer cells
When asked what ‘feeds’ cancer cells, Dr. Solanki noted that cancer cells need large amounts of nutrients, including glucose, amino acids, and nucleotides, to proliferate. While some of these nutrients can be synthesized inside cells, others, like amino acids, must be taken from dietary sources.
He continued that sensing pathways such as GATOR and mTORC1 detect nutrient levels and signal cellular mechanisms to divide, grow and proliferate.
“As body nutrients are influenced by diet, we found that feeding a low protein diet to animals created a demand versus supply crisis in colon cancer cells which resulted in massive cancer cell death,” he said.
“Thus, these cancers are metabolically vulnerable, and a low protein diet along with chemotherapy may kill cancer cells in these settings as their demand is high, and supply is low,” he noted.
“Feeding or starving cancer cells is clearly complicated, but this research shows that depriving certain amino acids influences the mTORC-1 pathways leading to cell death.”
— Dr. Jeffrey Nelson, surgical director at The Center for Inflammatory Bowel and Colorectal Diseases, Mercy Medical Center, Baltimore, who was not involved in the study, speaking to MNT
Limitations
When asked about the study’s limitations, Dr. Nelson pointed out that the research was carried out in mice and cancer cell lines, and said it still remained “unclear how this might be applied clinically in humans as of yet.”
Dr. Terrero added that clinical trials remain challenging due to patient compliance difficulties and controlling for lifestyle variables that may 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.
“As cancer patients often undergo muscle wasting, putting patients on long-term low protein won’t be ideal. As cancer cells are rapidly dividing, they may require increased nutrients to recover after chemotherapy regimens. Thus, giving low protein diets at key windows, like a week before/after chemotherapy, may synergize in eradicating these tumor cells with high demand.”
— Dr. Sumeet Solanki
He added that his team is now assessing if reducing specific amino acids could mimic the effects of low protein diets without negative side effects such as malnutrition and weight loss.
When asked about what these findings may mean for cancer treatment, Dr. Solanki said:
“Extrapolation of our findings in animal models to humans would be premature, although this is a small step in the right direction. We would strongly suggest consulting an oncologist and dietician for medical advice.”
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