Methylglyoxal / MAPK Cancer Research Results

MGO, Methylglyoxal: Click to Expand ⟱
Features:
Methylglyoxal is a reduced derivative of pyruvic acid that is produced by glycolysis and other metabolic pathways. It is involved in the formation of advanced glycation end products, DNA damage, and diabetes complications.

-Methylglyoxal is specifically inhibits OXPHOS in cancer cells ?
-Methylglyoxal in cancer cells inhibits GAPDH, an essential enzyme acting in the glycolsis pathway. GAPDH inhibition depletes ATP profoundly depriving the cancer cells of energy.
-Activator of GABA A receptor

Some research may indicate it can promote cancer growth.

Dose: (30-40mg/day) 7.5mg/kg 4 times/day (plus 400mg Vit C) + VitB complex twice/day
-Combine with curcumin(8g/d)?

Combine with:
Chitosan?
Creatine (30-60 mins before)
GLO1 inhibitors (Naringin, Curcumin)
Nrf2 inhibitors: (ex Ascorbic Acid)
GABA supplementation
Metformin?

Avoid combination with DCA?

Pathways
1. Glyoxalase System Glyoxalase I and II: (glyoxalase system) which detoxifies methylglyoxal. In many cancers, the expression of glyoxalase I (and sometimes glyoxalase II) is upregulated. This allows tumor cells to tolerate higher MG levels resulting from their altered metabolism (often enhanced glycolysis), protecting them from dicarbonyl stress while simultaneously supporting their survival and proliferation.

2. Advanced Glycation End Products (AGEs) and RAGE Pathway
AGE Formation:-Supplemented MG can increase the formation of advanced glycation end products (AGEs) RAGE Activation:AGEs can lead to the activation of RAGEE, which include the activation of NF-κB and MAPK pathways.

3. NF-κB Signaling Pathway: The activation of NF-κB by MG-induced AGE-RAGE signaling

4. MAPK Pathway: can be activated as a result of MG-induced oxidative and dicarbonyl stress
.
5. ROS Generation and Oxidative Stress
Methylglyoxal can raise intracellular ROS levels. (reinforcing the pro-tumorigenic environment.) -excessive ROS can be deleterious.

Sources: Western or Chinese chemical suppliers under CAS number 78-98-8


MAPK, mitogen-activated protein kinase: Click to Expand ⟱
Source: CGL-CS
Type:
Mitogen-activated protein kinases (MAPKs) are a group of proteins involved in transmitting signals from the cell surface to the nucleus, playing a crucial role in various cellular processes, including growth, differentiation, and apoptosis (programmed cell death).

MAPK Pathways: The MAPK family includes several pathways, the most notable being:
1.ERK (Extracellular signal-Regulated Kinase): Often associated with cell proliferation and survival.
2.JNK (c-Jun N-terminal Kinase): Typically involved in stress responses and apoptosis.
3.p38 MAPK: Associated with inflammatory responses and apoptosis.

Inhibitors: Targeting the MAPK pathway has become a strategy in cancer therapy. For example, BRAF inhibitors (like vemurafenib) are used in treating melanoma with BRAF mutations.
Altered Expression Levels:
Overexpression: Many cancers exhibit overexpression of MAPK pathway components, such as RAS, BRAF, and MEK. This overexpression can lead to increased signaling activity, promoting cell proliferation and survival.
Downregulation: In some cases, negative regulators of the MAPK pathway (e.g., MAPK phosphatases) may be downregulated, leading to enhanced MAPK signaling.
The expression levels of MAPK pathway components can serve as biomarkers for cancer diagnosis, prognosis, and treatment response. For example, high levels of phosphorylated ERK (p-ERK) may indicate active MAPK signaling and poor prognosis in certain cancers.

Numerous reports indicate that the MAPK pathway plays a major role in tumor progression and invasion, while inhibition of MAPK signaling reduces invasion.


Scientific Papers found: Click to Expand⟱
1890- MGO,    The Dual-Role of Methylglyoxal in Tumor Progression – Novel Therapeutic Approaches
- Review, Var, NA
AntiCan?, TumCG↓, GAPDH↓, Apoptosis↑, TumCCA↑, MAPK↑, Bcl-2↓, MMP9↓, eff↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Core Metabolism/Glycolysis

GAPDH↓, 1,  

Cell Death

Apoptosis↑, 1,   Bcl-2↓, 1,   MAPK↑, 1,  

Cell Cycle & Senescence

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

TumCG↓, 1,  

Migration

MMP9↓, 1,  

Drug Metabolism & Resistance

eff↑, 1,  

Functional Outcomes

AntiCan?, 1,  
Total Targets: 9

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: MAPK, mitogen-activated protein kinase
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:123  Target#:181  State#:%  Dir#:2
wNotes=0 sortOrder:rid,rpid

 

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