Leucine-rich Diet may Fuel Breast Cancerís Drug Resistance

by Colleen Fleiss on  April 18, 2019 at 1:14 PM Cancer News
RSS Email Print This Page Comment bookmark
Font : A-A+

Relationship between the amino acid leucine and tamoxifen resistance has been identified by scientists at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC).
Leucine-rich Diet may Fuel Breast Cancerís Drug Resistance
Leucine-rich Diet may Fuel Breast Cancerís Drug Resistance

About one in eight women in the United States will develop breast cancer in her lifetime. The vast majority of these cancers rely on the hormone estrogen to grow. Estrogen-receptor positive (ER+) breast cancer tumors are frequently treated with the drug tamoxifen, which blocks the hormone's effect on the tumor. However, many tumors eventually become resistant to tamoxifen, allowing cancer to recur or metastasize.

Led by Senthil K. Muthuswamy, PhD, the researchers further identified a key protein that imports leucine into cells and modulates sensitivity to tamoxifen in ER+ cells in the lab setting. The findings, published today in the journal Nature, reveal a potential new strategy for overcoming resistance to endocrine drugs in ER+ breast cancer patients.

"Patients with ER+ breast cancer who develop endocrine-resistant and metastatic cancer have very poor life expectancy, usually less than five years survival, because they have limited treatment options available," said Muthuswamy, who is Director of the Cell Biology Program and Deputy Director of Translational Research in the Cancer Research Institute at BIDMC. "Our findings in the lab demonstrate that decreasing leucine levels suppresses proliferation of tumor cells, whereas increasing leucine enhances it. Furthermore, the findings open up the possibility that a low-leucine diet could be beneficial for patients with ER+ breast cancer."

Leucine is one of the 20 amino acids - the building blocks of all proteins in our body - and is among the 9 essential amino acids that must be obtained via food. Beef, chicken, pork and fish are all rich sources of leucine. Because cells can't produce leucine on their own, Muthuswamy and colleagues were able to test how manipulating levels of leucine in cells cultured in a dish would affect the growth of human derived ER+ breast cancer cells. The researchers reported that decreasing leucine levels suppressed ER+ breast cancer cells' division, while a tenfold increase of the amino acid enhanced it.

"Because animal proteins have higher amount of leucine compared to plant proteins, this study begins to identify a diet intervention strategy to help patients with ER+ breast cancers," said Muthuswamy. "Our research does not imply that animal proteins will enhance growth of breast cancer cells - only that lowering leucine levels can be beneficial for patients diagnosed with ER+ breast cancer."

Surprisingly, the scientists also discovered that cells that were induced to become resistant to tamoxifen gained the ability to grow despite low levels of leucine. Further investigation revealed that a protein on the surface of cells, called SLC7A5, required for ferrying leucine into the cell, is present at higher levels in cells resistant to tamoxifen. Increasing the levels of SLC7A5 allows cells to absorb more leucine and was sufficient to make breast cancer cells resistant to tamoxifen and inhibiting SL7A5 using chemical inhibitor was sufficient to shrink ER+ tumors in mice. Muthuswamy believes inhibiting SLC7A5 could be a potential therapeutic approach in the treatment of ER+ breast cancers.

"Before this research, there was no reason to expect that estrogen biology has anything to do with affecting intracellular levels of leucine in cells," said first author, Yasuhiro Saito, PhD, a research fellow in the Department of Medicine and Pathology at BIDMC. "We have uncovered a new area of estrogen receptor biology, which will lead to new strategies to help patients with endocrine resistant breast cancer."

Even so, the discovery is in keeping with previous reports that decreasing overall leucine intake can lead to better metabolic health, Muthuswamy added. Decreasing the amount of total protein in the diet is known to improve metabolic health and longevity in rodent studies. Recent studies in human and mice demonstrated that that a low leucine diet can provide similar benefits. While protein restriction can make it difficult to meet daily nutrient requirements, a diet made-up of low- leucine plant proteins may be a better alternative for patients with ER+ breast cancer.

"A properly controlled clinical study to assess clinical benefit of actively decreasing leucine intake in diet during treatment for ER+ breast cancer will be of significant value because a positive outcome can provide a simple intervention strategy that can help us better care for patients with endocrine-sensitive and resistant breast cancer," Muthuswamy said.

Source: Eurekalert

Post a Comment

Comments should be on the topic and should not be abusive. The editorial team reserves the right to review and moderate the comments posted on the site.
Notify me when reply is posted
I agree to the terms and conditions
Advertisement

Recommended Reading

More News on:

Diet Pills Drug Toxicity Low Carbohydrate Diet Atkins Diet The Cabbage Diet South Beach Diet Mastitis Negative Calorie Diet Bulimia Nervosa Why Do We Eat - Nutrition Facts 

News A - Z

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z

News Search

Medindia Newsletters

Subscribe to our Free Newsletters!

Terms & Conditions and Privacy Policy.

Stay Connected

  • Available on the Android Market
  • Available on the App Store

News Category

News Archive