There are 20+ amino acids needed for building protein. All it takes is for one to be in short supply to cause a reduction in the growth factor IGF-I. Omnivores might be able to reduce their intake of whole protein, I suppose, but vegans would find it easier to selectively restrict a single amino acid. IGF-I is an important PCa growth factor.
[1] Gary Meadows, at Washington State U, has spent a number of years looking at the feasibility of selective restriction. I will limit quotes from his papers, since his account of the effects on cells gets very technical.
[1a] (2001) "Specific Amino Acid Deficiency Alters the Expression of Genes in Human Melanoma and Other Tumor Cell Lines".
"Studies in humans and rodents suggest that restriction of tyrosine (Tyr) and phenylalanine (Phe) could become a very important addition to antineoplastic therapies. Dietary restriction of these amino acids is not toxic to healthy humans and it enhances natural killer cell cytolytic activity, increases T-lymphocyte numbers and decreases the activation of platelets, which could retard metastasis (1). In fact, dietary Tyr and Phe restriction specifically inhibits metastasis of melanoma, leukemia, hepatocarcinoma and lung carcinoma in rodents ..."
"Recently, a number of metastasis suppressor genes have been identified. One of these ... (MKK4/SEK1), is a gene that suppresses metastasis of prostate cancer ..."
"... data indicate clearly that deprivation of Tyr and Phe regulates MKK4/SEK1 protein expression ... and that the regulation is cell-type specific. Although it is not clear whether MKK4/SEK1 protein is a target for cancer therapy, the fact that amino acid deficiency modulates MKK4/SEK1 protein expression ... suggests that nutrients play an important role in regulation of cancer progression."
[1b] (2003)
"Here we studied the effect of deprivation of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), ... on human DU145 and PC3 androgen-independent prostate cancer cells ..."
"Deprivation of the amino acids similarly inhibited growth of DU145 and PC3 cells, arresting the cell cycle ..."
"Met and Tyr/Phe deprivation induces {cell death} in DU145, but only Met deprivation induces {cell death} in PC3 cells."
"Tyr/Phe and Met deprivation inhibits invasion of DU145 and PC3, but Gln deprivation only inhibits invasion of DU145 cells."
"This study shows the potential for specific amino acid restriction to treat prostate cancer."
[1c] (2006) "Selective amino acid restriction targets mitochondria to induce {cell death} of androgen-independent prostate cancer cells."
"Relative specific amino acid dependency is one of the metabolic abnormalities of cancer cells, and restriction of specific amino acids induces {cell death} of prostate cancer cells."
"This study shows that restriction of tyrosine and phenylalanine (Tyr/Phe), glutamine (Gln), or methionine (Met), ... affects the function of mitochondria in DU145 and PC3" cells. These changes induce cell death in the PCa cells.
[1d] (2008) "Selective Amino Acid Restriction Differentially Affects the Motility and Directionality of DU145 and PC3 Prostate Cancer Cells"
[1e] (2011) "Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells."
"In DU145 cells, Gln and Met restriction increased glucose consumption and decreased lactate production, but Tyr/Phe restriction did not."
"In PC3 cells, all amino acid restrictions reduced glucose consumption and lactate production."
[2] Methionine Restriction.
Amino acids have activity apart from building protein. Methionine, for instance, is a methyl donor in one-carbon metabolism. PCa cells like to be hypermethylated. This is how tumor suppressor genes are silenced.
Some years ago my integrative medicine doctor advised me to inject vitamin B12. My homocysteine was high & I had zero cobalt in a hair sample. I was taking B12 orally, but seemingly lacked enough intrinsic factor for uptake.
For 4 straight months, my PSA, which had been constant for 6 straight months, rose. That's when I learned of the SAM cycle & the protective effect of low B12. Which is actually the protective effect of methionine restriction. B12 is needed to convert homocysteine back to methionine.
In 1974, a paper was published that described the effect of replacing methionine with homocysteine in cell growing medium. Normal cells thrived but cancer cells did not. [2a] It seems that PCa cells might want methionine itself - not just the methyl it carries.
It is important, I feel, to realize that, while methionine is found in food, most of the methionine in the body at any point in time, has come from recycled homocysteine.
The conversion of homocysteine to methionine is associated with the B vitamins. Folate (B9) generally acts as the methyl donor. B12, as mentioned, is an essential cofactor. In countries where grains are fortified with folic acid, methyl deficiency is rare. In other countries, diets may have an insufficiency of folate - or can be made so.
[2b] Some here may be familiar with Michael Greger. He is in charge of propaganda for veganism. LOL. I say this because, for him, it's a cause rather than a lifestyle option. And, although he uses published studies, he cherry-picks. & it seems that none of us would ever have ever become ill (any disease) if we had been vegans.
Anyway, veganism is a not uncommon response to a cancer diagnosis, & Greger does have a number of videos (2c) that might help those who are interested. There is spin, sometimes outrageously so, but I respect him for using published studies which one can take the trouble to read.
It was natural for him to make a video [2b] on methionine restriction for cancer, because the main dietary sources are chicken & fish. Plants have low levels. He doesn't mention egg whites, which are high.
He makes no mention of restricting the regeneration of methionine from homocysteine. Presumably because no animals are sacrificed in that process.
-Patrick
[1a] jn.nutrition.org/content/13...
[1b] ncbi.nlm.nih.gov/pubmed/127...
[1c] ncbi.nlm.nih.gov/pubmed/168...
[1d] ncbi.nlm.nih.gov/pmc/articl...
[1e] ncbi.nlm.nih.gov/pmc/articl...
[2a] ncbi.nlm.nih.gov/pmc/articl...
