I have always been interested in ways in which a treatment might be enhanced by supplements or dietary changes. (or repurposed drugs)
In this case, "depletion of L-cysteine/cystine" was via "an engineered human enzyme, Cyst(e)inase".
"PCa cells treated with Cyst(e)inase lead to DNA single and double strand breaks resulted from clustered oxidative DNA damage (SSBs and DSBs)."
which is useful when treatment includes a PARP inhibitor, say.
But cysteine deficiency can be engineered via dietary changes.
Cysteine is largely obtained from fully-formed protein (e.g. meat):
"Cysteine utilized in the body is derived from dietary cysteine and methionine, sulfur-containing amino acids (SAAs) that are largely obtained from digested protein. Since mammals obtain cysteine both directly from the diet and by degradation of dietary methionine, the normal cysteine requirement can be satisfied from dietary sources." [2]
Vegans may unintentionally become deficient.
"Conclusions: The current results demonstrate the importance of oxidative DNA damage either alone or in combination for Cyst(e)inase-induced anticancer activity. Furthermore, cysteine/cystine depletion alters the tumor immune landscape favoring enhanced immune checkpoint inhibition targeting PD-L1. Thus, combinatorial approaches with Cyst(e)inase could lead to novel therapeutic strategies for PCa." [1]
Curiously, Cystein seems to be the single amino acid with a significant average range departure in the study linked below. (Atho' the median between the groups was near identical.) Since it was 3 x higher in the PCa study population (vs non-PCa controls), it would seem to support your paper. I was expecting to see that methionine was also elevated, but that was not the case - and was actually lower in the PCa group. (Table from the study is attached.)
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ABSTRACT
There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed. Several metabolites, which deserve special attention in the further metabolomic investigations on searching for prostate cancer markers, were indicated. Moreover, free amino acid profiles enabled to classify samples to one of the studied groups with high sensitivity and specificity. The presented research provides a strong evidence that ethanolamine, arginine and branched-chain amino acids metabolic pathways can be a valuable source of markers for prostate cancer. The altered concentrations of the above-mentioned metabolites suggest their role in pathogenesis of prostate cancer and they should be further evaluated as clinically useful markers of prostate cancer.
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Full paper is here:
Amino Acid Profiles of Serum and Urine in Search for Prostate Cancer Biomarkers: a Pilot Study, Int J Med Sci 2017; 14(1):1-12.
If PCa wants high levels of cystine {cystine is the oxidized derivative of the amino acid cysteine (Wiki)}, that is easy in omnivores {cystine is common in many foods such as eggs, meat, dairy products, and whole grains (Wiki)}.
Methionine is a different issue, in that methionine is largely dependent on the recycling of homocycsteine.
One of my early blunders was B12 injections due to elevated homocysteine.
SAM is the universal methyl donor in the body. When SAM delivers its methyl, we are left with homocysteine. For homocysteine to be recycled back to methionine, we need a dietary methyl donor - commonly folate, but folic acid works too. There are cofactors required for this and B12 is one of them.
PCa cells are avid for methyl. The promotor regions for tumor suppressor genes are usually methylated. The cancer needs to be hypermethylated and the result is a drop in available methionine if the SAM system can't keep up.
Methione is a good amino acid target. Unfortunately, the FDA mandated that commom grain products be fortified with folic acid. While many countries followed the U.S. lead, many did not. In the U.S., one would have to give up bread & rice, etc. to limit methyl intake - or limit cofactor intake.
It seems that my stomach does not produce sufficient 'intrinsic factor' for B12 uptake. In addition, I drink wine & scotch every day & that leads to lower B12 levels. So I tend to have low SAM production & high homocysteine.
Incidentally, while elevated homocysteine is associated with cardiovascular events, interventions to reduce homocysteine do not reduce the risk of further events. So homocysteine might not be the bad actor in CVD,
Patrick - I have long considered you the resident expert on the SAMe cycle and methylation in general. And since metabolism offers a most actionable avenue for us as we seek ways to outsmart our cancers, those are both critical functional elements in creating a strategy to do so.
In the above reply you commented that:
"PCa cells are avid for methyl. The promotor regions for tumor suppressor genes are usually methylated. The cancer needs to be hypermethylated and the result is a drop in available methionine if the SAM system can't keep up."
That would seem to correlate with the low methionine results in the PCa group as indicated the the table - as their cancer cells were using more than in the controls.
Since the EU countries are much more restrictive of GMO foods (and at least require labeling), I look for grain products that are imported from EU countries. I have also wondered if those products, say the German-made Swedish Wasa Crisp Bread you introduced me to, are required to be fortified with folic acid for import into the US? Nothing on the label indicates that is the case.
As for the wine and Scotch, we all have our personal pleasures without which life would be much less enjoyable. This one's for you and your occasional lunch partner - Salute!
Folks, I know its been a while, but thought I would try to put together a low meth- diet. Switching from brwn rice to undoctored pasta, off fish, cheese, sunflower and nuts, (almonds may be ok) off most beans, and having more cooked greens. I hear barley is ok, so looking for a source. Not sure abt the avocado at lunch, or the B12 in cocoa and almond milks. I will substitute CBD for wine and cannabis flower for scotch. Cheers!
Interesting...this could at least partially explain why statistically low animal proteins or vegan diets tend to give statistically better results with PCa
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