GSTZ1 Cancer Research Results

GSTZ1, Glutathione S-transferase zeta 1: Click to Expand ⟱
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Type:
GSTZ1 (Glutathione S-transferase zeta 1) is an enzyme involved in phase II detoxification and tyrosine catabolism.

Several studies have reported differences in GSTZ1 expression across cancer types. In some malignancies, GSTZ1 expression is downregulated, which might diminish the cell's ability to detoxify carcinogens and reactive oxygen species (ROS). In other instances, GSTZ1 expression may be upregulated, possibly reflecting an adaptive response to increased oxidative stress or drug exposure.

-Enzyme responsible for conversion of DCA to its inactive metabolite, glyoxylate, is downregulated in liver cancer and upregulated in some breast cancers, leading to abnormal expression of the protein.
(desireable to inhibit GSTZ1 to reduce resistance to DCA)
Scientific Papers found: Click to Expand⟱
6683- DCA,    Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts
- Review, Var, NA
PDK1↓, classic DCA target, pyruvate dehydrogenase kinase
lactateProd↓, reduce lactic acid production which would push the cell towards oxidative phosphorylation: this would be the supposed function of dichloroacetate (DCA).
Apoptosis↑, They found that DCA induced apoptosis and decreased proliferation by restoring mitochondrial oxidative metabolism, without toxicity to normal cells.
TumCP↓,
selectivity↑,
other↝, many clinics, usually called “DCA Clinics” have opened, mainly in Canada and Germany.
Dose↝, DCA is sold over the counter and is produced by many laboratories. The quality of the product from these laboratories is not well established. These particulars explain many of the doubts about DCA’s real value as a therapeutic tool.
BioAv↑, DCA is an orally available molecule that is quickly and almost completely absorbed by the digestive system
Half-Life↓, With a 10 mg/kg infusion the maximum plasma concentration achieved was between 19.9 μg/ml and 24.7 μg/ml with a half life of only 20 minutes. If the infused dose was increased to 20 mg/kg the plasma concentration was between 57.3 and 74.9 μg/ml with
Glycolysis↓, facilitates the switch from a glycolytic to an oxidative metabolism.
OXPHOS↑,
Casp↑, onversion to an oxidative metabolism by DCA, is an increase in caspase-mediated apoptosis
i-pH↓, pHi decreases (at least temporarily).
COX2↑, DCA increases the expression of COX2 and the latter increases tumor resistance to DCA. Therefore, a possible integrated treatment could be COX2 inhibitor co-administered with DCA
Hif1a↓, DCA suppresses HIF-1α activity and angiogenesis through the inhibition of PDK-II
angioG↓,
HMG-CoA↓, figure 7
GSTZ1↓,
OCR↑,
lipoGen↓,
fatigue↓,
survivin↓, Survivin (an inhibitor of apoptosis) expression was decreased and miR-375 (a microRNA which acts as a tumor suppressor) levels were increased.
miR-375↑,
eff↓, African Americans are known to respond poorly to therapy compared with Caucasian American patients.
CSCs↓, DCA can inhibit the cancer stem cell like characteristics of the cells and strongly influenced the metabolic pathway of the cells causing a shift from glycolysis to oxidative phosphorylation.
TumAuto↑, DCA induced autophagy in human colon cancer cells with ROS production and mTOR inhibition,
mTOR↓,
TumCI↓, DCA induced apoptosis, inhibited invasion, and angiogenesis. In mouse experiments in vivo with the melanoma allografts, DCA reduced volume and weight of tumors.
TumVol↓,
TumW↓,
ATP↓, DCA alone reduced glycolytic activity and intracellular ATP levels and inhibited cellular growth in melanoma cells.
Warburg↓, DCA was also found to interrupt the Warburg effect and decreased proliferation.
eff↑, The co-application of metformin and DCA suppressed human liver cancer cell proliferation inducing apoptosis through inhibition of mTORC1 and increased ROS in vitro and in vivo
e-pH↑, when measuring extracellular pH in vivo found that an initial increase in extracellular pH of tumors in mice when treated with DCA.
eff↑, To avoid the development of this type of metabolic resistance DCA should be given simultaneously with other metabolic drugs such as metformin [327] or 2 deoxyglucose.
eff↑, chronic co-administration of DCA with sodium bicarbonate to tumor bearing mice prolonged survival
other↝, High doses of thiamin (vit B1) have effects similar to those of DCA: reduced PDH phosphorylation, reduced lactate prod and increased casp3 activity with reduced proliferation in colon cancer cells. can vitB1 replace DCA as a nontoxic PDK inhibitor?
RadioS↑, Dong et al. [380] found that DCA radiosensitized esophageal carcinoma cells in vitro and in vivo through increased ROS accumulation.
toxicity↓, 25 mg/Kg/day may show a mild sedative effect or drowsiness. The most serious published side effect is reversible peripheral neuropathy
Dose↝, 10 to 50 mg/kg body weight/day has been found to be a safe dose. However, single nucleotide polymorphisms (SNPs) in the gene of the enzyme GSTZ1 cause difficulties in establishing a universal dose [409] as noted above.
eff↑, There is strong evidence showing that the association of metformin and DCA has significant cytotoxic effects.
eff↑, To this approach we must add a third compound: a COX2 inhibitor like celecoxib to decrease COX2 expression induced by DCA.
eff↑, the triple association of DCA, metformin and celecoxib, which has never been experimentally tested in patients, deserves well planned phase II clinical trials.
toxicity↝, DCA will never become a stand-alone chemotherapeutic compound. The fundamental reason for this statement is that the drug can only reach micromolar blood concentrations without toxicity and requires millimolar levels to be cytotoxic.
eff↓, DCA should not be used in association with allopurinol, NSAIDs, or flavonoids because they reduce cellular DCA uptake.


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:


NA, unassigned(tgid=0) ⓘ

miR-375↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

GSTZ1↓, 1,   OXPHOS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   OCR↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Glycolysis↓, 1,   HMG-CoA↓, 1,   lactateProd↓, 1,   lipoGen↓, 1,   PDK1↓, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   Casp↑, 1,   survivin↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↝, 2,  

Autophagy & Lysosomes(tgid=9) ⓘ

TumAuto↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CSCs↓, 1,   mTOR↓, 1,  

Migration(tgid=13) ⓘ

TumCI↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   Hif1a↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2↑, 1,  

Cellular Microenvironment(tgid=17) ⓘ

e-pH↑, 1,   i-pH↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   Dose↝, 2,   eff↓, 2,   eff↑, 6,   Half-Life↓, 1,   RadioS↑, 1,   selectivity↑, 1,  

Functional Outcomes(tgid=23) ⓘ

fatigue↓, 1,   toxicity↓, 1,   toxicity↝, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 37

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: GSTZ1, Glutathione S-transferase zeta 1
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#:1203  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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