Targeting Glutamine Metabolism

[pjoshea13]

New paper below [1a]. Full text: [1b].

First, a few notes.

"Studies have indicated the importance of glutamine in certain tumors. For example, the inhibition of glutamine metabolism was reported to prevent growth of several tumors such as breast, liver, kidney and T-cell lymphoblastic leukemia." Wiki: [2].

Glutamine is a nonessential amino acid (the body can make it), but it becomes conditionally-essential if demand becomes very high - as, potentially, with PCa.

As a building block of protein, one would need to avoid fully-formed protein when attempting a glutamine-restrictive diet, but it is plentiful in other foods too [3]:

The following are the percentages of protein made up of L-glutamine in each high-glutamine food:

Eggs: 4.4% (0.6 g per 100 g of eggs)

Beef: 4.8% (1.2 g per 100 g of beef)

Skim milk: 8.1% (0.3 g per 100 g of milk)

Tofu: 9.1% (0.6 g per 100 g of tofu)

White rice: 11.1% (0.3 g per 100 g of rice)

Corn: 16.2% (0.4 g per 100 g of corn)

& here are 200 vegetables low in glutamine [4].

(#20 ketchup - Richard Nixon's favorite vegetable!)

Range:

#1 Ginger (3mg in 1 tsp)

to #100 Sweet Red Bell Peppers (251mg in 1 medium)

to #200 Stirfried Soybean Sprouts (1968mg in 100 grams) - which is not low at all, imo!

From the new paper:

"Prostate cancer has increasingly been characterized as a tumor type that is heavily dependent on glutamine for growth and survival. In this review, we highlight the preclinical evidence that supports a relationship between glutamine signaling and prostate cancer progression. We focus on the regulation of glutamine metabolism in prostate cancer through key pathways involving the androgen receptor pathway, MYC, and the PTEN/PI3K/mTOR pathway. We end with a discussion on considerations for translation of targeting glutamine metabolism as a therapeutic strategy to manage prostate cancer.

"Here, it is important to understand that the tumor microenvironment also plays a role in facilitating glutamine signaling and resultant prostate cancer growth. The druggability of prostate cancer glutamine metabolism is more readily achievable with our greater understanding of tumor metabolism and the advent of selective glutaminase inhibitors that have proven safe and tolerable in early-phase clinical trials."

Oddly, I only found 29 prior papers for on PubMed.

Metformin (& berberine) might be helpful in regulating glutamine [5] [6].

-Patrick

[1a] pubmed.ncbi.nlm.nih.gov/369...

[1b] imrpress.com/journal/FBE/15...

[2] en.wikipedia.org/wiki/Gluta...

[3] healthline.com/nutrition/gl...

[4] tools.myfooddata.com/nutrie...

[5] scielo.isciii.es/scielo.php...

[6] dovepress.com/berberine-inh...

[Scout4answers]

Berberine…another one of those no brainers : unknown potential that seems logical to use but also low risk.

[witantric in reply to Scout4answers]

is Berberine a supplement?

[Scout4answers in reply to witantric]

yes, on Amazon

[Captain_Dave in reply to Scout4answers]

Does berberine lower glutamine? Or do you take because it is anti-cancer?

[Scout4answers in reply to Captain_Dave]

I am not currently taking it but have purchased it and intend to take it during my much anticipated ADT vacation around the end of this year.

[Kuanyin]

I believe we had a similar discussion several years ago and came to the conclusion that it was not practical to limit glutamine. Even though it's non-essential, when cancer cells need it they find it. However, there are other ways to attack the problem such as the one cited below.

Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism

Npj/Precision oncology, June 5, 2017

Abstract

High-throughput screening of a natural compound library was performed to identify the most efficacious combinatorial treatment on prostate cancer. Ursolic acid, curcumin and resveratrol were selected for further analyses and administered in vivo via the diet, either alone or in combination, in a mouse allograft model of prostate cancer. All possible combinations of these natural compounds produced synergistic effects on tumor size and weight, as predicted in the screens. A subsequent untargeted metabolomics and metabolic flux analysis using isotopically labeled glutamine indicated that the compound combinations modulated glutamine metabolism. In addition, ASCT2 levels and STAT3, mTORC1 and AMPK activity were modulated to a greater extent by the combinations compared to the individual compounds. Overall, this approach can be useful for identifying synergistic combinations of natural compounds for chemopreventive and therapeutic interventions.

Among the "winners" are curcumin, ursolic acid and resveratrol taken together.

K.

[Spyder54]

This site is so progressive. Thank you Patrick.

If you have seen any of the many vieos of Dr Thomas Seyfried out of Boston College, you quickly learn that he believes Ca is first damage at a cellular level to the mitochondria, then evolves to become a genetic mutational disease.

He strongly believes that by lowering Glutamine & Glucose, you can strengthen the Mitochondria. This can prevent the Metastisis process. He says he cannot cure Cancer, but believes he can prevent the Metastisis process which is what ultimately kills us. Lowering Glucose is easy, he says with a Keto diet, or even with Metformin pharmacology therapies that diabetics take. Lowering Glutamine is harder. He talks about “DON” to lower Glutamine. You mention Berberine above. This ties in with what you have said above, with PubMed to back it.

It does feel like there is something to this. Mike