New U.S. cell study below [1].
Studies show that vegan populations have a higher occurrence of various deficiencies. It's a diet that requires a certain amount of education & discipline to get right. But this also makes it an attractive diet for selective nutrient restriction.
Methionine is an essential amino acid [2].
It is possible to get enough from the diet, but mostly we don't - & don't need to, since the body can recycle homocysteine back to methionine.
Methionine is the starting point for the SAM (SAMe) cycle. Methionine is converted to SAM, the universal methyl donor in the body. When SAM drops off its methyl, we are left with homocysteine. Methyl donors in the diet can be used to convert homocysteine back to methionine.
PCa cells are invariably hypermethylated. The promoter regions for tumor suppressor genes are commonly methylated (silenced). Methyl restriction along with a demethylation agent is an attractive strategy for reactivation of tumor suppressor genes.
The recycling of homocysteine, for many of us depends on vitamins B6, B9 & B12. B9 is folate, which is the common methyl donor. (Folic acid is a synthetic supplement that can convert to folate.) B6 & B12 are necessary cofactors in the conversion of homocysteine to methionine.
In the U.S. & many other countries, folic acid is added to grains. It can therefore be difficult for those who eat bread or rice to avoid folic acid. But, I believe, the more obscure grains, such as spelt, are not fortified. U.S. food labels clearly identify fortified foods.
Vegans quite often do not get enough B12. However, it can take years for the body's reserves to be depleted. Older men sometimes produce little or no intrinsic factor, which is required for B12 uptake, so may be close to deficiency, if not actually deficient. Outright deficiency is dangerous, since the harm done cannot be reversed, but borderline deficiency may interfere with the production of methionine.
From the new paper:
"Cancer cells require elevated amounts of methionine (MET) and arrest their growth under conditions of MET restriction (MR). This phenomenon is termed MET dependence."
"When the human PC-3 prostate carcinoma cell line was cultured in MET-free, homocysteine-containing (MET-HCY+) medium, there was an extreme increment in DNA content without cell division indicating that the cells were blocked in S phase."
"... S-phase-dependent chemotherapy drugs, which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil (5-FU) ... were highly effective in killing the cancer cells. In contrast, treatment of cancer cells with drugs in the presence of MET, only led to the majority of the cancer cell population being blocked in G0/G1 phase ... The G0/G1 blocked cells were resistant to the chemotherapy."
"MR has the potential for highly effective cell-cycle-based treatment strategy for cancer in the clinic."
Methionine restriction might be a good idea wnen undergoing chemotherapy.
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/307...
Methods Mol Biol. 2019;1866:49-60. doi: 10.1007/978-1-4939-8796-2_5.
Tumor-Specific S/G2-Phase Cell Cycle Arrest of Cancer Cells by Methionine Restriction.
Hoffman RM1,2, Yano S3,4.
Author information
1
AntiCancer, Inc., San Diego, CA, USA. all@anticancer.com.
2
Department of Surgery, University of California, San Diego, CA, USA. all@anticancer.com.
3
AntiCancer, Inc., San Diego, CA, USA.
4
Department of Surgery, University of California, San Diego, CA, USA.
Abstract
Cancer cells require elevated amounts of methionine (MET) and arrest their growth under conditions of MET restriction (MR). This phenomenon is termed MET dependence. Fluorescence-activated cell sorting (FACS) first indicated that the MET-dependent SV40-transformed cancer cells were arrested in the S and G2 phases of the cell cycle when under MR. This is in contrast to a G1-phase accumulation of cells, which occurs only in MET-supplemented medium at very high cell densities and which is similar to the G1 cell-cycle block which occurs in cultures of normal fibroblasts at high density. When the human PC-3 prostate carcinoma cell line was cultured in MET-free, homocysteine-containing (MET-HCY+) medium, there was an extreme increment in DNA content without cell division indicating that the cells were blocked in S phase. Recombinant methioninase (rMETase) treatment of cancer cells also selectively trapped cancer cells in S/G2: The cell cycle phase of the cancer cells was visualized with the fluorescence ubiquitination cell cycle indicator (FUCCI). At the time of rMETase-induced S/G2-phase trap, identified by the cancer cells' green fluorescence by FUCCI imaging, the cancer cells were administered S-phase-dependent chemotherapy drugs, which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil (5-FU) and which were highly effective in killing the cancer cells. In contrast, treatment of cancer cells with drugs in the presence of MET, only led to the majority of the cancer cell population being blocked in G0/G1 phase, identified by the cancer cells becoming red fluorescent in the FUCCI system. The G0/G1 blocked cells were resistant to the chemotherapy. MR has the potential for highly effective cell-cycle-based treatment strategy for cancer in the clinic.
KEYWORDS:
Arrest; Cancer cells; Cell cycle; Methionine dependence; Methionine restriction; S/G2 phase, chemotherapy
PMID: 30725407 DOI: 10.1007/978-1-4939-8796-2_5
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S-Adenosylmethionine (SAM/SAMe) affects ERK1/2 and STAT3 pathway in androgen-independent prostate cancer cells
