MGMT Cancer Research Results

MGMT, O^6^-methylguanine-DNA methyltransferase: Click to Expand ⟱
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MGMT (O^6^-methylguanine-DNA methyltransferase) is a DNA repair enzyme that plays a crucial role in protecting the genome from alkylating damage. Key points include:
-MGMT repairs DNA lesions by removing alkyl groups from the O^6^-position of guanine, thereby preventing mutations.
-It is a “suicide enzyme,” meaning that it is inactivated after repairing one lesion.
-By counteracting the cytotoxic effects of alkylating agents, MGMT is a critical determinant of cell survival following exposure to such chemotherapeutic agents.

In several cancers, the MGMT promoter is hypermethylated. This epigenetic modification suppresses MGMT expression and has several implications:
-Reduced MGMT levels lead to an accumulation of DNA damage.
-Increased mutation rates can contribute to cancer initiation and progression.

MGMT expression levels in tumors have a significant impact on the response to alkylating agents (e.g., temozolomide in glioblastoma).
-High MGMT Expression: Can confer resistance to these drugs by effectively repairing the induced DNA damage.
-Low MGMT Expression: Often observed in tumors with MGMT promoter hypermethylation, making the cancer cells more susceptible to chemotherapeutic agents.

Improved Prognosis with Low MGMT Expression in Specific Contexts (high MGMT activity can allow tumor cells to recover from DNA damage).
Scientific Papers found: Click to Expand⟱
2663- AL,    Therapeutic Effect of Allicin on Glioblastoma
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG
BioAv↝, After processing, such as cutting, crushing, chewing, or dehydration, alliinase rapidly breaks down alliin to form allicin. Allicin is immediately decomposed to other organosulfur compounds such as diallyl sulphide (DAS), diallyl disulfide(DADS), and
TumCCA↑, The results show DATS can reduce tumor growth by inhibits cell cycle progression and promotes p53-mediated tumor suppression pathways
P53↑,
HDAC↓, The findings demonstrate that DATS can inhibit U87MG cell growth in vivo by inhibiting HDAC [10].
CSCs↓, Inhibition of cancer stem cells(CSC)
ROS↑, DATS can induce apoptosis by ROS through regulation of Bcl-2 and have anticancer effect on human glioblastoma (U87MG) and neuroblastoma (SH-SY5Y) cells
ChemoSen↑, The most interesting thing is allicin can enhance the sensitivity of TMZ-resistant cells to TMZ by inhibiting MGMT expression.
MGMT↓,

278- ALA,    The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment
- Review, NA, NA
ROS↑, direct anticancer effect of the antioxidant ALA is manifested as an increase in intracellular ROS levels in cancer cells
NRF2↑, enhance the activity of the anti-inflammatory protein nuclear factor erythroid 2–related factor 2 (Nrf2), thereby reducing tissue damage
Inflam↓,
frataxin↑,
*BioAv↓, Oral ALA has a bioavailability of approximately 30% due to issues such as poor stability in the stomach, low solubility, and hepatic degradation.
ChemoSen↑, ALA can enhance the functionality of various other anticancer drugs, including 5-fluorouracil in colon cancer cells and cisplatin in MCF-7 breast cancer cells
Hif1a↓, it is inferred that lipoic acid may inhibit the expression of HIF-1α
eff↑, act as a synergistic agent with natural polyphenolic substances such as apigenin and genistein
FAK↓, ALA inhibits FAK activation by downregulating β1-integrin expression and reduces the levels of MMP-9 and MMP-2
ITGB1↓,
MMP2↓,
MMP9↓,
EMT↓, ALA inhibits the expression of EMT markers, including Snail, vimentin, and Zeb1
Snail↓,
Vim↓,
Zeb1↓,
P53↑, ALA also stimulates the mutant p53 protein and depletes MGMT
MGMT↓, depletes MGMT by inhibiting NF-κB signalling, thereby inducing apoptosis
Mcl-1↓,
Bcl-xL↓,
Bcl-2↓,
survivin↓,
Casp3↑,
Casp9↑,
BAX↑,
p‑Akt↓, ALA inhibits the activation of tumour stem cells by reducing Akt phosphorylation.
GSK‐3β↓, phosphorylation and inactivation of GSK3β
*antiOx↑, indirect antioxidant protection through metal chelation (ALA primarily binds Cu2+ and Zn2+, while DHLA can bind Cu2+, Zn2+, Pb2+, Hg2+, and Fe3+) and the regeneration of certain endogenous antioxidants, such as vitamin E, vitamin C, and glutathione
*ROS↓, ALA can directly quench various reactive species, including ROS, reactive nitrogen species, hydroxyl radicals (HO•), hypochlorous acid (HclO), and singlet oxygen (1O2);
selectivity↑, In normal cells, ALA acts as an antioxidant by clearing ROS. However, in cancer cells, it can exert pro-oxidative effects, inducing pathways that restrict cancer progression.
angioG↓, Combining these two hypotheses, it can be hypothesized that ALA may regulate copper and HIF-2α to limit tumor angiogenesis.
MMPs↓, ALA was shown to inhibit invasion by decreasing the mRNA levels of key matrix metalloproteinases (MMPs), specifically MMP2 and MMP9, which are crucial for the metastatic process
NF-kB↓, ALA has been shown to enhance the efficacy of the chemotherapeutic drug paclitaxel in breast and lung cancer cells by inhibiting the NF-κB signalling pathway and the functions of integrin β1/β3 [138,139]
ITGB3↓,
NADPH↓, ALA has been shown to inhibit NADPH oxidase, a key enzyme closely associated with NP, including NOX4

3371- QC,    Quercetin induces MGMT+ glioblastoma cells apoptosis via dual inhibition of Wnt3a/β-Catenin and Akt/NF-κB signaling pathways
- in-vitro, GBM, T98G
TIMP2↑, MMP2, and MMP9 was significantly decreased by quercetin treatment, while TIMP1 and TIMP2 were upregulated (
TumCG↓, Quercetin significantly suppressed the growth and migration of human GBM T98G cells, induced apoptosis, and arrested cells in the S-phase cell cycle
TumCMig↓,
Apoptosis↑,
TumCCA↑,
MMP↓, collapse of mitochondrial membrane potential, ROS generation, enhanced Bax/Bcl-2 ratio, and strengthened cleaved-Caspase 9 and cleaved-Caspase 3 suggested the involvement of ROS-mediated mitochondria-dependent apoptosis in the process
ROS↑,
Bax:Bcl2↑,
cl‑Casp9↑,
cl‑Casp3↑,
DNAdam↑, quercetin-induced apoptosis was accompanied by intense DNA double-strand breaks (DSBs), γH2AX foci formation, methylation of MGMT promoter, increased cleaved-PARP, and reduced MGMT expression
γH2AX↑,
MGMT↓,
cl‑PARP↑,


Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

frataxin↑, 1,   NRF2↑, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

NADPH↓, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   Apoptosis↑, 1,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   Casp9↑, 1,   cl‑Casp9↑, 1,   Mcl-1↓, 1,   survivin↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   MGMT↓, 3,   P53↑, 2,   cl‑PARP↑, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   GSK‐3β↓, 1,   HDAC↓, 1,   TumCG↓, 1,  

Migration ⓘ

FAK↓, 1,   ITGB1↓, 1,   ITGB3↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   Snail↓, 1,   TIMP2↑, 1,   TumCMig↓, 1,   Vim↓, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   ChemoSen↑, 2,   eff↑, 1,   selectivity↑, 1,  
Total Targets: 47

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ROS↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,  
Total Targets: 3

Scientific Paper Hit Count for: MGMT, O^6^-methylguanine-DNA methyltransferase
1 Allicin (mainly Garlic)
1 Alpha-Lipoic-Acid
1 Quercetin
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#:%  Target#:1087  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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