Can switching to a low-protein diet help starve tumors?

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Researchers are investigating the effect diet has on cancer growth. Kaat Zoetekouw/Stocksy
  • 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 further studies are needed to see if the findings 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 US in 2022 and 8.6% of cancer deaths.

Studies show that nutrient-sensing molecules known as mTORC1 contribute to tumor growth and is hyperactivated in about more than 70% of human cancers, including colon cancer. Animals surveys demonstrate that inhibition of mTORC1 inhibits tumor growth.

Although drugs that inhibit the mTORC1 signaling pathway have been shown to be clinical 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 can inhibit tumor growth by reducing mTORC1.

Further research into how dietary protein restriction affects mTORC and tumor growth may 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 chemotherapy synergizes to kill cancer cells,” Dr. Sumeet Solanki, research scientist in Molecular and Integrative Physiology at the University of Michigan, first author of the study, said Medical News Today.

The study was published in Gastroenterology.

The researchers first assessed colon cancer cells in mice. They found that mTORC1 activation was higher in the presence of amino acids.

The researchers then investigated how these results translated to living mice. To do so, they assessed the effects of a low-protein diet on mouse models of colon cancer for two weeks, followed by one month of chemotherapy. While mouse food typically consists of 21% protein, they fed mice only 4% protein.

They found that mice on a low-protein diet showed 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 then found that a low-protein diet—and specifically reduction of 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.

From testing human colon cancer biopsies, the researchers also found that several genetic markers for 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 the Miami Cancer Institute, part of Baptist Health South Florida, who was not involved in the study, said Medical News Today:

“[This study implies] that colon tumor cells can 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 exploited by limiting the intake of amino acids – via dietary protein restriction – and thus trigger tumor cell stress and death.”

“[The] results also suggest that alterations in amino acid sensing pathways may drive chemotherapy resistance. [Therefore]dietary protein restriction could potentially reduce drug resistance to standard chemotherapy in colorectal cancer.”
— Dr. Gretel Terrero

However, she added that further research is needed to understand the exact molecular pathways that drive tumor growth and resistance.

When asked what ‘feeds’ cancer cells, Dr. Solanki that cancer cells need large amounts of nutrients, including glucose, amino acids and nucleotides, to multiply. 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.

“Since body nutrients are affected by diet, we found that feeding a low-protein diet to animals created a demand versus supply crisis in colon cancer cells, resulting in massive cancer cell death,” he said.

“Thus, these cancers are metabolically vulnerable, and a low-protein diet along with chemotherapy can 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 affects the mTORC-1 pathways that lead to cell death.”
– Dr. Jeffrey Nelson, director of surgery at the Center for Inflammatory Bowel and Colorectal Diseases, Mercy Medical Center, Baltimore, who was not involved in the study, speaks to MNT

When asked about the study’s limitations, Dr. Nelson noted that the research was conducted in mice and cancer cell lines, and said it is still “unclear how this can be applied clinically to humans yet.”

Dr. Terrero added that clinical trials remain challenging due to patient compliance issues and controlling for lifestyle variables that can 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.

Caveats about a low-protein diet for cancer patients

“Since cancer patients often go through muscle wasting, it would not be ideal to put patients on long-term low-protein diets. Since cancer cells divide rapidly, they may require increased nutrients to recover from chemotherapy regimens. Giving low-protein diets at key windows, like a week before/after chemotherapy, can thus help eradicate these high-demand tumor cells.”
— Dr. Sumeet Solanki

He added that his team is now evaluating whether reducing specific amino acids can mimic the effects of low-protein diets without negative side effects such as malnutrition and weight loss.

When asked what these results might mean for cancer treatment, Dr. Solanki:

“Extrapolating our findings in animal models to humans would be premature, although this is a small step in the right direction. We would strongly recommend that you consult an oncologist and dietitian for medical advice.”

Can switching to a low-protein diet help starve tumors?

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