How does Glutamine feed Cancer? Part 1
Dr. Kevin Conners – a review of recent literature
Cancer cells exhibit an increased level of aerobic glycolysis with accumulation of lactic acid, a phenomenon known as the Warburg effect . Apparently, survival of cancer cells requires an elaborate system for acid resistance along with acid production via waste from metabolism. L-glutamine has long been known to be essential for cancer cell growth and this series of articles may shed some light on that mechanism .
One recent finding has proven that glutamine provides acid resistance for E. coli through release of ammonia. One might hypothesize that the primary use of glutamine by cancer cells is to it help them survive in their acid environment rather than provide nutrition. An enzyme, glutaminase, attracted to the presence of glutamine, helps cancer cells overcome the harshness of the acidic environment and allows continued growth .
Certain glutaminase inhibitors, currently under clinical trials as an anti-cancer drug, may work by countering the ability of cancer cells to adapt under such an acidic environment.
Glutamine is an amino acid found in most consumed proteins and abundant in the human body. Cancer cells heavily depend on it for growth most tumor cells consume glutamine at a much higher rate compared to normal cells . The common view has been that glutamine provides carbon and nitrogen source for cell growth as it is converted into glutamate and ammonia through a process called glutaminolysis, which then generates ATP (energy) and lactate.
In their published paper, Lu P, Ma D, Chen Y, et al., explain a novel bacterial acid resistance system, which relies on the release of ammonia from glutamine via activity of glutaminase enzymes. The released ammonia neutralizes the acid in E. coli. This finding, together with the use of ammonia by Helicobactor polari to fight acid in the stomach , may reveal a different role of glutamine in cancer cell survival.
In summary, while glutamine may provide a direct fuel source for growing cancer, it also may aide its survival by helping it resist acid. Two different glutaminase enzymes (GLS) have been identified in mammalian cells: GLS1 (with two splice forms KGA and GAC), which is mainly expressed in the kidney, and GLS2 (also called LGA), which exists mainly in the liver [9,10]. The mRNA levels of GAC have been found to be elevated in various tumors and was shown to be “essential for the growth of non-small cell lung cancer” . Glutaminase inhibitors have been under clinical trials in the United States as a potential anti-cancer therapy .
It may behoove us to explore natural ways to reduce glutamine and glutamate in cancer patients such as reducing protein in their diets and elimination of exogenous, food-source glutamates. Natural compounds that may function as glutaminase inhibitors or help scavenge excess glutamates may include Graviola, EGCg (from green tea extract), Sulforaphane (from broccoli seed extract), Magnolia Bark Extract, Dashen Root, Honokiol, Valerian, Golden Larch and Curcumin (from turmeric).
Find the Glutamate Scavenger HERE.
- Warburg O. Science. 1956. pp. 309–314.
- Tannock IF, Rotin D. Cancer Res. 1989. pp. 4373–4384
- Medina MA. J Nutr 2001131(9 Suppl)2539S–2542S.Discussion 2550S–2531S.
- Lu P, Ma D, Chen Y, et al. Cell Res. 2013. pp. 635–644.
- Eagle H. Science. 1955. pp. 501–514.
- Medina MA, Sanchez-Jimenez F, Marquez J, et al. Mol Cell Biochem. 1992. pp. 1–15.
- DeBerardinis RJ, Cheng T. Oncogene. 2010. pp. 313–324.
- Montecucco C, Rappuoli R. Nat Rev Mol Cell Biol. 2001. pp. 457–466
- Curthoys NP, Kuhlenschmidt T, Godfrey SS, et al. Arch Biochem Biophys. 1976. pp. 162–167.
- Elgadi KM, Meguid RA, Qian M, et al. Physiol Genomics. 1999. pp. 51–62.
- Aledo JC, Gomez-Fabre PM, Olalla L, et al. Mamm Genome. 2000. pp. 1107–1110.
- van den Heuvel AP, Jing J, Wooster RF, et al. Cancer Biol Ther. 2012. pp. 1185–1194.
- Rajagopalan KN, DeBerardinis RJ. J Nucl Med. 2011. pp. 1005–1008.