Scientists are increasingly looking into the effects of diet on cancer growth. Researchers have studied the effects of a low-protein diet on colon cancer growth.
They found that a low-protein diet reduced tumor growth and increased cancer cell death in mice. According to the researchers, further studies are needed to determine whether these findings apply to humans. Colon cancer occurs when cells in the colon or rectum grow out of control.
Studies show that nutrient-sensing molecules known as mTORC1 contribute to tumor growth and are overactivated in approximately more than 70% of human cancers, including colon cancer. Animal studies demonstrate that inhibition of mTORC1 inhibits tumor growth. Although drugs that inhibit the mTORC1 signaling pathway have been shown to be clinically effective, their use is limited because tumors often return following treatment ends and side effects include immunosuppression.
Studies show that amino acids activate mTORC1, and that dietary protein restriction can inhibit tumor growth by reducing mTORC1. Further research into how dietary protein restriction affects mTORC and tumor growth might improve cancer treatments. Recently, researchers investigated the effects of low-protein diets on mTORC1 activation in animal and human tissue models.
Researchers have observed that feeding human-derived colon cancer cells low in amino acids and treating them with chemotherapies results in a synergy to kill the cancer cells. The study was published in Gastroenterology.
Limit proteins to inhibit tumors
The researchers first evaluated colon cancer cells in mice. They found that mTORC1 activation was higher in the presence of amino acids. The researchers then looked at how these results translated to live mice. To do this, they evaluated the effects of a low-protein diet on mouse models of colon cancer for two weeks, followed by a month of chemotherapy. While the mice’s diet typically contains 21% protein, they fed mice a diet containing only 4% protein. They found that mice on a low-protein diet had less early tumor growth and more cancer cell death than control mice. These mice also showed reduced mTORC1 activation and proliferation. The researchers noted that this suggests that amino acids regulate mTORC1 activity and that limiting amino acids might inhibit early tumor growth. Using in vitro tests, the researchers then discovered that a diet low in protein and more particularly a reduction in the amino acids leucine and cystine, modified the nutritional signals transmitted to mTORC1 via the protein complexes GATOR1 and GATOR2. When amino acids are abundant, GATOR2 activates mTORC1. In contrast, when amino acids are low, GATOR1 deactivates mTORC1.
Only certain patients can benefit from it
By testing human colon cancer biopsies, the researchers also found that more mTORC1 genetic markers correlated with resistance to chemotherapy and poorer outcomes. The researchers therefore suggested that screening for amino acid-sensing genes might help determine which patients would benefit from a low-protein diet and which others would not.
This study implies that colon tumor cells can alter the way amino acids are sensed to further activate mTORC1, leading to increased cell growth and tumor cell proliferation. One might take advantage of the hyperactivity of mTORC1 by limiting the supply of amino acids, via the restriction of dietary proteins, and thus trigger stress and death of tumor cells.
The results also suggest that changes in amino acid sensing pathways may lead to resistance to chemotherapy drugs. Therefore, dietary protein restriction might potentially decrease resistance to standard chemotherapy drugs in colorectal cancer. She adds, however, that more research is needed to understand the exact molecular pathways that drive tumor growth and resistance.
What feeds cancer cells
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, such as amino acids, must come from dietary sources. Sensing pathways such as GATOR and mTORC1 detect nutrient levels and signal cellular machinery to divide, grow and proliferate. Because the body’s nutrients are influenced by diet, researchers found that feeding animals a low-protein diet created a demand-versus-supply crunch in colon cancer cells, which which led to the massive death of cancer cells.
Thus, these cancers are metabolically vulnerable, and a low-protein diet combined with chemotherapy can kill cancer cells under these conditions because demand is high and supply is low.
Feeding or starving cancer cells is clearly complicated, but this research shows that deprivation of certain amino acids influences mTORC-1 pathways leading to cell death.
Limits
This study was conducted on mice and cancer cell lines, and it is not yet clear how this might be applied clinically in humans. Clinical trials remain challenging due to patient compliance issues and the consideration of lifestyle variables that may affect the tumor microenvironment.
Another difficulty, if the results of the study are promising, a low-protein diet may not be the long-term solution. As cancer patients often experience muscle wasting, putting them on a low protein diet long term will not be ideal. Since cancer cells divide rapidly, they may need increased amounts of nutrients to recover from chemotherapy regimens. Thus, giving low protein diets at key windows, such as a week before/following chemotherapy, may have synergy in eradicating these high-demand tumor cells. »
