GSTZ1 Cancer Research Results

GSTZ1, Glutathione S-transferase zeta 1: Click to Expand ⟱
Source:
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⟱
6681- DCA,    Dichloroacetate (DCA) in Cancer Care
PDK1↓, Specifically, it inhibits pyruvate dehydrogenase kinase, which may convert metabolism from fermentative glycolysis back to oxidative phosphorylation.
Apoptosis↑, This process may induce cancer cell apoptosis through several mechanisms including increased oxidative stress and reduced lactate levels.
ROS↑,
lactateProd↓,
Dose↝, DCA can be administered orally or intravenously.
eff↝, overall, there is insufficient evidence to support the efficacy of DCA as a cancer treatment.
toxicity↓, most studies have found DCA to be reasonably safe and well tolerated, The most common side effect is reversible peripheral neuropathy.
NP/CIPN↑, One of the five patients who entered the trial with some degree of peripheral neuropathy developed a score of 3 in the Total Neuropathy Score (TNS), but this resolved within six months after DCA cessation
Dose↝, doses range from 10-50mg/kg daily, with the most common oral dosing being 6.25-12.5mg/kg taken twice daily.
*BioAv↑, DCA is a small water soluble molecule of 150 Da, allowing it to achieve 100% bioavailability when given either orally or intravenously
*Half-Life↓, Serum DCA levels rise rapidly after oral administration and exhibit a relatively short half-life. elimination half-life of 92 minutes
GSTZ1↝, DCA metabolism is affected by glutathione transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI) genotype status. Individuals with at least one wild-type haplotype metabolize DCA more rapidly and thus may be able to tolerate a higher dose
Glycolysis↓, DCA acts on the mitochondrial matrix of cancer cells, diverting metabolism from fermentative glycolysis back to oxidative phosphorylation
OXPHOS↑,
MPT↑, reopening of voltage and redox sensitive mitochondrial transition pores (22). This allows for the pro-apoptotic mediators, cytochrome c and apoptosis-inducing-factor, to be released into the cytoplasm,
Cyt‑c↑,
AIF↑,
Casp↑, increasing the levels of pro-apoptotic ROS through the activation of caspases
CSCs↓, Although less well established, there is some evidence that DCA may be able to reduce stemness and induce differentiation in cancer stem cells
Remission↑, rigorous treatment cycle with DCA, alpha lipoic acid, and B vitamins and achieved complete remission of his cancer as evidenced by PET scans, CT scans, and laboratory testing. Four years later, the patient remained cancer free.
ChemoSen↑, Several preclinical studies have demonstratedsynergistic effects of DCA with chemotherapeutic agents, including carboplatin (34, 57), oxaliplatin (34, 57), 5-fluorouracil (29), paclitaxel (58, 59), doxorubicin (60), elesclomol (24), and sorafenib (6
RadioS↑, There is preliminary preclinical evidence that DCA may act as a radiosensitizer primarily by increasing levels of reactive oxygen species in tumour cells
toxicity↑, Combined with artesunate one patient experienced fatal liver and bone marrow toxicity.


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:


Redox & Oxidative Stress(tgid=1) ⓘ

GSTZ1↝, 1,   OXPHOS↑, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

AIF↑, 1,   MPT↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

Glycolysis↓, 1,   lactateProd↓, 1,   PDK1↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   Casp↑, 1,   Cyt‑c↑, 1,  

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

CSCs↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   Dose↝, 2,   eff↝, 1,   RadioS↑, 1,  

Functional Outcomes(tgid=23) ⓘ

NP/CIPN↑, 1,   Remission↑, 1,   toxicity↓, 1,   toxicity↑, 1,  
Total Targets: 20

Pathway results for Effect on Normal Cells:


Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↑, 1,   Half-Life↓, 1,  
Total Targets: 2

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#:4
  wNotes=on  sortOrder:rid,rpid

 

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