DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications

[sammamish]

ncbi.nlm.nih.gov/pmc/articl...

Here is a most recent summary paper on DNA methylation by Mahmood et al June 2019. Good explanations, however I am a little confused by the statement at the end about possible therapeutic role of SAM. I was under the impression SAM was a huge methyl donor and therefore to be avoided? Any one here capable of deciphering this?

"The expression of MBD2 gene was downregulated when the cancer cells were treated with the naturally occurring methyl group donor SAM that shows anti-proliferative and anti-metastatic effects (143, 144). This approach is particularly attractive because SAM is non-toxic to cancer cells and has been shown to cause downregulation of several other oncogenes and prometastatic genes without changing the expression of the known tumor suppressor genes in vitro and in vivo (278). "

[Hidden]

Dear sammamish .this is way over my head ..but are you talking about Sam-e ??

[pjoshea13 in reply to Hidden]

Same as SAMe.

en.wikipedia.org/wiki/S-Ade...

-Patrick

[Hidden in reply to pjoshea13]

Brother I admire your work and research . I’ve been on the Sam-e per my nat dr for over a year with great results for my moods and even cut muscle and joint pain also to nil. Feel less lethargy too. My dr says that since I’m not eating meat there is no negative connotation for me with Sam-e.. for me it’s a god send. I’m no expert . But I follow Dr. Uzick and his methods of nutrition . Peace to you today brother. Thanks for the post .,.

[pjoshea13]

It certainly is confusing.

"Our group has previously shown that the treatment of cancer cells with the universal methyl group donor S-adenosylmethionine (SAM) downregulates MBD2 expression and shows anti-proliferative and anti-metastatic effects both in vitro and in vivo (143, 144)."

Says two things: (i) SAM is the universal methyl donor in the body & (ii) paradoxically, the team has previously shown SAM to be therapeutic.

But they warn that: "... caution must be taken while targeting MBD2 to avoid any potential negative ramification"

From (143) [1]:

"We tested the hypothesis that cell invasiveness and tumorigenesis are driven by hypomethylation of genes involved in tumor progression."

It has been widely reported that PCa cells are usually hypermethylated. Methylation of the promoter regions for tumor suppressor genes is a common epigenetic change. In the U.S. population, as well as others where grains are fortified with folic acid, hypomethylation must be uncommon.

However, giving a patient SAM (SAMe) in such cases is a two-edged sword - useful genes may be activated, while tumor-suppressor genes might be silenced. Is this a "potential negative ramification"?

-Patrick

[1] cancerres.aacrjournals.org/...

[FCoffey]

Like many or most treatments, a lot depends on the individual patient.

This is one of the many reasons I get upset when I hear the words "standard of care." In my brain I hear "Same damn thing we do to everyone." But that is another rant.

One of my issues is MTHFR, a genetic mutation that compromises the body's ability to methylate. This quite possibly contributed to my cancer, but I didn't know about it until I started this journey. Few doctors know about MTHFR, but the ones who do tell me that I probably methylate at about 20% of what "normal" people do.

So I take supplements to add methyl vitamins, and try to avoid things like folic acid which is basically poisonous to me.

So for me I suspect that adding methyls is beneficial, but it is certainly possible that it would not be helpful for some other people.

[sammamish]

I am confused, I thought folate was a facilitator of methylation?