Mannose effects on colon cancer - novel mechanism

[cs3000]

https://spiral.imperial.ac.uk/bitstream/10044/1/65247/2/Merged%20PDF.pdf

https://www.nature.com/articles/s41586-018-0729-3

I think the mechanism is unlike normal cells (within reason) some cancers can't metabolise mannose effectively. So they get overwhelmed by the mannose increase, cant use glucose effectively & it acts as a way to hinder/destroy them.

The effect relies on levels of the PMI enzyme (phosphomannose-isomerase) as normal cells with decent pmi convert the mannose to a fructose. colon cancer with low pmi should be very suitable.
+ in the high PMI tumors high amounts of mannose itself might lower PMI by depleting the enzyme,/ overwhelm what the enzyme can process (but then this might effect healthy cells negatively too)

Phosphomannose Isomerase High Expression Associated with Better Prognosis in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The need for increased patient survival has not been met for PDAC. The addition of mannose to conventional chemotherapy leads to accumulation ...

www.ncbi.nlm.nih.gov

Mannose and phosphomannose isomerase regulate energy metabolism under glucose starvation in leukemia - PubMed

Diverse metabolic changes are induced by various driver oncogenes during the onset and progression of leukemia. By upregulating glycolysis, cancer cells acquire a proliferative advantage over normal hematopoietic cells; in addition, these changes in energy metabolism contribute to anticancer...

pubmed.ncbi.nlm.nih.gov

effect size @ 20% mannose in drinking water worked better than chemo"therapy"
(and likely with way less toxicity / downsides "importantly, mannose had no negative impact on the health or weight of the animals over the time examined")

also lowers the number of tumors

And if someone combined this with :
. very low pufa + low-moderate fat diet
. lipolysis/fatty acid inhibition +
. lipogenesis inhibition (high in cancer cells Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids mainly utilizing glutamine i think and 1 other i cant remember) / fatty acid synthase inhibitors e.g some polyphenols

then i bet the effect size would be way better
(as glucose utilization would be blocked by mannose + then fatty acids would be too , so the cancer cells would mainly have lactate to rely on, but very little fuel to use considering glucose & fats are the main fuels, the problem is you'd have to pick a mannose dose that wouldnt hinder glucose utilization by healthy cells this way for more of a selective effect on low pmi cancers)

Cancer cells with low MPI levels are unable to catabolize efficiently mannose-6-phosphate, which accumulates intracellularly and impairs glucose utilization

As mannose did not reduce intracellular glucose, but significantly impacted cell growth, we considered it may interfere with glucose metabolism. We also observed that mannose does not produce much lactate (indicating it is poorly metabolised) and more importantly, that mannose markedly reduces lactate production from glucose. mannose treatment not only affects pools of glycolytic intermediates, but also those involved in the TCA cycle, pentose phosphate pathway and glycan synthesis

mannose in doses around a couple grams daily doesn't hinder regular cell function,
actually it stimulates mitochondria respiration mildly & helps colitis ~2.5g human dose
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381535/

 

[Rinse & rePeat]

“D-mannose is being increasingly used as an effective alternative to antibiotics for various conditions. A simple sugar, d-mannose is found naturally in high amounts in many fruits such as apples, oranges, and peaches, as well as blueberries and cranberries. Vegetables, including green beans, cabbage, and broccoli, are also a common source. In addition, d-mannose occurs naturally in some cells in the human body and is thought to be a prebiotic, because consumption of d-mannose stimulates and fosters the growth of good bacteria in the digestive tract.”


Chemically, d-mannose is considered a simple sugar. Structurally, it is similar to glucose, but it is absorbed more slowly in the gastrointestinal tract. This accounts for its lower glycemic index. Compared with actual glucose, which is readily absorbed and has a glycemic index of 100, mannose must first be converted into fructose and then into glucose, significantly blunting the insulin response and reducing its impact on blood sugar levels. After mannose is absorbed by the gut, it is not stored in the liver like glucose but is filtered out of the body directly by the kidneys. “

https://www.clinicaladvisor.com/home/features/alternative-meds-update/d-mannose-an-effective-antibiotic-alternative/#:~:text=Cranberries%20are%20a%20natural%20source,well%20as%20blueberries%20and%20cranberries.

 

[aliml]

Zinc is an essential cofactor for PMI activity.

...Zinc ion chelator TPEN clearly increased the response of mannose-insensitive cells to mannose by inhibiting enzyme activity of PMI, while zinc supplement could effectively reverse this effect.

ZIP10 is a negative determinant for anti-tumor effect of mannose in thyroid cancer by activating phosphate mannose isomerase - Journal of Experimental & Clinical Cancer Research

Background Mannose, a natural hexose existing in daily food, has been demonstrated to preferentially inhibit the progression of tumors with low expression of phosphate mannose isomerase (PMI). However, its function in thyroid cancer still remains elusive. Methods MTT, colony formation and flow...

jeccr.biomedcentral.com

...PMI can be inhibited by silver ions. This process is shown to be irreversible,

Mechanism of irreversible inactivation of phosphomannose isomerases by silver ions and flamazine - PubMed

Silver ions and silver-containing compounds have been used as topical antimicrobial agents in a variety of clinical situations. We have previously shown that the enzyme phosphomannose isomerase (PMI) is essential for the biosynthesis of Candida albicans cell walls. In this study, we find that...

pubmed.ncbi.nlm.nih.gov

...Silver ions induce transient release of intracellular zinc,

Silver ions induce oxidative stress and intracellular zinc release in human skin fibroblasts - PubMed

Silver compounds used as topical antimicrobial agents are known to exert toxic effects on skin cells. The aim of this study was to investigate whether the toxicity of silver ions, in analogy to other transition metal ions, depends on pro-oxidant effects. We treated human skin fibroblasts with...

pubmed.ncbi.nlm.nih.gov