Nature: resistance to breast cancer may be related to a diet rich in leucine!

April 18, 2019 / BIOON / - about one eighth of American women will have breast cancer in their lifetime Most breast cancers rely on estrogen to grow Estrogen receptor positive (ER +) breast cancer is often treated with tamoxifen, a drug that blocks the effects of hormones on tumors However, many tumors eventually develop resistance to tamoxifen, which leads to cancer recurrence or metastasis Photo source: nature now, a team of researchers at the Beth Israel Deaconess Medical Center (bidmc) cancer center have found an unexpected relationship between leucine levels and the development of tamoxifen resistance in ER + breast cancer Under the leadership of Dr senthil K muthuswamy, the researchers further identified a key protein that can transfer leucine into cells and regulate the sensitivity of ER + breast cancer cells to tamoxifen The relevant research results were recently published in nature This study revealed a potential new strategy to overcome the endocrine drug resistance of ER + breast cancer patients "ER + breast cancer patients who develop drug-resistant and metastatic tumors have a very short survival, usually less than five years, because of their limited choice of treatment," said muthuswamy, director of cell biology programs and deputy director of transformation research at the BIDMC Cancer Institute "Our findings in the laboratory show that lowering leucine level can inhibit the proliferation of tumor cells, while increasing leucine level can enhance the proliferation of cancer cells." In addition, these findings provide evidence for the potential benefits of a low leucine diet Leucine is one of the 20 amino acids that make up all the proteins in human body, and it is also one of the nine essential amino acids that must be obtained through food Beef, chicken, pork and fish are rich in leucine Since the cells themselves do not produce leucine, muthuswamy and his colleagues were able to test how controlling leucine levels affects the growth of human derived ER + breast cancer cells Lowering leucine levels inhibits ER + breast cancer cell division, which is enhanced by a tenfold increase in amino acids, the researchers said "Because animal proteins contain more leucine than plant proteins, this study helps to find a dietary intervention strategy to help ER + breast cancer patients," muthuswamy said "Our study doesn't mean that animal protein promotes the growth of breast cancer cells - it's just that lowering leucine levels is good for patients diagnosed with ER + breast cancer." Surprisingly, scientists have also found that cells resistant to tamoxifen can still grow at low leucine levels Further studies have shown that slc7a5, a protein on the cell surface, is necessary for the transport of leucine into the cell, which is higher in cells resistant to tamoxifen Increasing slc7a5 level can make the cells absorb more leucine, which is enough to make breast cancer cells resistant to tamoxifen, while inhibiting sl7a5 with chemical inhibitors can reduce ER + tumor in mice "Before this study, we had no reason to think that the biology of estrogen had anything to do with affecting intracellular leucine levels," said Dr Yasuhiro Saito, lead author of the study and a researcher in the medical and pathological Department of bidmc "We have identified a new area of estrogen receptor biology that will lead to new strategies to help patients with endocrine resistant breast cancer." Muthuswamy added However, this finding is consistent with previous reports that reducing total leucine intake can improve metabolic health In rodent studies, reducing the amount of total protein in the diet can improve metabolic health and longevity Recent studies in humans and mice have shown that a low leucine diet offers similar benefits Due to the limitation of protein, it is difficult to meet the daily nutritional needs, so the diet composed of low leucine plant protein may be a better choice for ER + breast cancer patients In the next study, muthuswamy's team is looking at whether limiting leucine in the diet can prevent the growth of ER + breast cancer cells in mice or enhance their response to treatment Reference: sentil K muthuswamy et al Llgl2 reserves rural stress by promoting leucine uptake in ER + burst cancer, nature (2019) Doi: 10.1038/s41586-019-1126-2