• Patients with ER+ breast cancer who develop endocrine-resistant and metastatic cancer have very poor life expectancy
  • There are limited treatment options available for ER+ breast cancer patients
  • Decreasing diet leucine levels suppresses ER+ breast cancer cells’ division

Primary Information, Benefits, and Important Facts on Leucine – Leucine is an essential amino acid meaning it can’t be produced by our body and must be obtained from food(1). Leucine is one of the three branched chain amino acids (BCAAs) together with isoleucine and valine, that have an important role in protein synthesis and muscle building(1). Leucine activates mTOR (a protein kinase that regulates protein synthesis and cell growth), which then induces muscle protein synthesis via S6K (a serine/threonine kinases involved in signal transduction); while on the other hand isoleucine and valine also activate mTOR, but are much weaker (2)(3). This is illustrated by the fact that 5g of leucine will be more effective than 5g mixed BCAAs in muscle binding(2). BCAAs are found in beef, chicken breast, salmon, eggs etc.(1). Other important benefits of Leucine include:

  • Decrease muscle soreness
  • Reduce exercise fatigue
  • Prevent muscle wasting
  • Improve health in people with cirrhosis, a chronic disease in which the liver does not function properly
Fig.1. Group of important proteins, meats, fish, dairy, eggs, white meat on a wooden table as background, Shot from above. Image adapted from (6).

The unexpected link between estrogen biology in ER+ breast cancer cells and intracellular level of leucine – About one in eight women in the United States will develop breast cancer in her lifetime (4). Estrogen-receptor positive (ER+) breast cancer, rely on the hormone estrogen to grow. Hence, tamoxifen which blocks the hormone’s receptors is used to treat ER+ breast cancer patients (4)(5). However, many tumors eventually become resistant to tamoxifen. This favors recurrence or metastasis of (ER+) breast cancer (6).

The researchers identified a key protein on the surface of cells, called SLC7A5 responsible to import leucine intracellularly (7). Increasing the levels of SLC7A5 allowed breast cancer cells to absorb more leucine and made them more resistant to tamoxifen (5). According to researchers at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) diets high in leucine do not act to fuel breast cancer but lowering leucine levels can be beneficial for patients diagnosed with ER+ breast cancer (8). Also, according to the research published in Nature, inhibiting SL7A5 using a chemical inhibitor was sufficient to shrink ER+ tumors in mice. (5)(7).


Fig.2. Senthil K. Muthuswamy, PhD, of the Cancer Center at Beth Israel Deaconess Medical Center. [BIDMC]. Image adapted from (8).

 The researchers at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) are already investigating whether a diet low in leucine can help to prevent ER+ tumor growth or boost response to therapy in mouse models. Hopefully, this research marks a new area of estrogen biology which will lead to new strategies to help patients with endocrine-resistant breast cancer.

COPYRIGHT: This article is the property of We Speak Science, a non-profit institution co-founded by Dr. Detina Zalli and Dr. Argita Zalli. The article is written by Rina Mehmeti, University of Prishtina, Kosovo.

References:

  1. https://www.healthline.com/nutrition/benefits-of-bcaa#section7
  2. https://examine.com/supplements/leucine/
  3. https://www.sciencedirect.com/topics/food-science/leucine
  4. https://www.bidmc.org/about-bidmc/news/2019/04/leucine-and-tamoxifen-resistance
  5. https://hms.harvard.edu/news/fuel-drug-resistance
  6. https://news.harvard.edu/gazette/story/2019/05/dietary-link-found-to-drug-resistant-breast-cancer/
  7. https://www.nature.com/articles/s41586-019-1126-2
  8. https://www.genengnews.com/news/breast-cancer-drug-resistance-linked-to-diet-high-in-leucine/