GCLC Cancer Research Results
GCLC, Glutamate-Cysteine Ligase, Catalytic Subunit: Click to Expand ⟱
| Source: |
| Type: |
The GCLC gene (Glutamate-Cysteine Ligase, Catalytic Subunit) is a key regulator of glutathione synthesis, and its expression has been studied in various types of cancer.
GCLC gene has been found to be:
Amplified in 15% of breast cancer cases
Mutated in 5% of lung cancer cases
Deleted in 10% of prostate cancer cases
Methylated in 20% of colorectal cancer cases
|
Scientific Papers found: Click to Expand⟱
| - |
in-vivo, |
CRC, |
HCT116 |
|
|
|
- |
in-vitro, |
CRC, |
SW480 |
|
|
|
ChemoSen↑, combined treatment
Casp9↑,
Ferroptosis↑, activation of ferroptosis and suppression of β-catenin/Wnt-signaling pathways were the key mediators for the anti-cancer and chemosensitizing effects of andrographis.
Wnt/(β-catenin)↓,
FTL↑,
TP53↑,
ACSL5↑,
GCLC↑,
GCLM↑,
SAT1↑,
STEAP3↑,
ACSL5↑,
| - |
in-vitro, |
Pca, |
DU145 |
|
|
|
- |
in-vitro, |
Nor, |
MEF |
|
|
|
NRF2↑, Cytoplasmic Nrf2 was translocated to the nucleus at 1.5–2 h in DU-145 and MEF WT cells, but not MEF PERK −/− cells. BA treatment demonstrating BA-activated Nrf2
selectivity↑, but not MEF PERK −/− cells.
NQO1↑, , NQO1, GCLC, and HMOX-1. DU-145 cells treated with BA increased the expression of all three
gene
GCLC↑,
HO-1↑,
TumCP↓, BA activates Nrf2 and ARE explains how BA slows proliferation of DU-145 cells but does not
cause apoptosis
*neuroP↑, it seems to ameliorate AD pathology by preventing neurodegeneration in several brain regions;
*Aβ↓, it has been shown to inhibit Aβ oligomer aggregations and to exert antioxidant, anti-inflammatory, and anti-apoptotic effects
*antiOx↑,
*Inflam↓,
*ROS↓, ability of ferulic acid to prevent oxidative stress
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B),
*NLRP3↓, it also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), has been observe
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK?, inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK),
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen in a mouse model of hepatotoxicity by inhibiting the expression of toll like receptor 4 (TLR4),
*TLR4↓,
*PPARγ↑, ferulic acid upregulated PPARγ and Nrf2 expression in renal cells,
*NRF2↑,
*Fenton↓, Ferulic acid may also inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu),
*IronCh↑,
*MDA↓, a lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker
*HO-1↑, Ferulic acid has been found able to upregulate HO-1, thus increasing the production of bilirubin, which acts as an efficient ROS scavenger,
*Bil↑,
*GCLC↑, (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic acid
*GCLM↑,
*NQO1↑,
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*SOD↑, Indeed, it prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*Ca+2↓,
*lipid-P↓,
*PGE2↓,
*antiOx↑, antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy.
*Inflam↓,
*neuroP↑, neuroprotective strategy against AD due to its promising antioxidant and anti-inflammatory properties.
*NF-kB↓, inhibition of the nuclear factor kappa-B (NF-κ B), a key mediator of proinflammatory cytokine signaling pathway, which promotes the synthesis of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α), leading to neuroinflammation
*NLRP3↓, also inhibited the NLR pyrin domain-containing protein 3 (NLRP3) inflammasome
*iNOS↓, A down-regulation by ferulic acid of proinflammatory molecules, such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, IL-1β, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1),
*COX2↓,
*TNF-α↓,
*IL1β↓,
*VCAM-1↓,
*ICAM-1↓,
*p‑MAPK↓, Ferulic acid was also able to affect the mitogen activated protein kinases (MAPKs) pathway, by inhibiting the phosphorylation of MAPKs, including p38 and c-Jun N-terminal kinase (JNK)
*p38↓,
*JNK↓,
*IL6↓, reduction of proinflammatory cytokines (IL-1β, IL-6, TNF-α and IL-8) mRNA expression
*IL8↓,
*hepatoP↑, ferulic acid reduces the liver damage induced by acetaminophen
*RenoP↑, renal protective effects by enhancing the CAT activity and PPAR γ gene expression
*Catalase↑,
*PPARγ↑,
*ROS↓, it was able to scavenge free radicals, inhibit the generation of reactive oxygen species (ROS)
*Fenton↓, inhibit the generation of reactive oxygen species (ROS) through the Fenton reaction, acting as a chelator of metals (i.e., Fe and Cu)
*IronCh↑,
*SOD↑, increasing the activity of the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes
*MDA↓, lowering in the levels of malondialdehyde (MDA), a lipid peroxidation marker,
*lipid-P↓,
*NRF2↑, ferulic acid has been found associated to the modulation of several signaling pathways, and to an increased expression of the nuclear translocation of the transcription factor NF-E2-related factor (Nrf2)
*HO-1↑, Particularly, Nrf2 binds the antioxidant responsive element (ARE) in the promoter region of the heme oxygenase-1 (HO-1) gene,
*ARE↑,
*Bil↑, production of bilirubin, which acts as an efficient ROS scavenger, in human umbilical vein endothelial cells (HUVEC) under radiation-induced oxidative stress
*radioP↑,
*GCLC↑, HO-1 upregulation, an increased expression of other antioxidant genes, such as glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase regulatory subunit (GCLM), and NADPH quinone oxidoreductase-1 (NQO1) were induced by ferulic
*GCLM↑,
*NQO1↑,
*Half-Life↝, highest plasma concentration varies greatly depending on the investigated species: it is reached at 24 min and 2 min after ingestion in humans and rats, respectively
*GutMicro↑, ferulic acid esterified forms have been shown to act as a prebiotic, since they stimulate the growth of eubacteria, such as Lactobacilli and Bifidobacteria, in the human gastrointestinal tract, so preserving the homeostasis of gut microbiota,
*Aβ↓, ferulic acid was able to inhibit the aggregation of Aβ25–35, Aβ1–40, and Aβ1–42 and to destabilize pre-aggregated Aβ.
*BDNF↑, up-regulation of brain-derived neurotrophic factor (BDNF) gene were observed after treatment with ferulic acid
*Ca+2↓, prevented membrane damage, scavenged free radicals, increased SOD activity, and decreased the intracellular free Ca2+ levels, lipid peroxidation, and the release of prostaglandin E2 (PGE2);
*lipid-P↓,
*PGE2↓,
*cognitive↑, highlighted that ferulic administration (0.002–0.005% in drinking water) for 28 days improved the trimethyltin-induced cognitive deficit: an increase in the choline acetyltransferase activity was hypothesized as a possible mechanism of action.
*ChAT↑,
*memory↑, Another study showed that ferulic acid, administered intragastrically (30 mg/kg) for 3 months, improved memory in the transgenic APP/PS1 mice, and reduced Aβ deposits,
*Dose↝, 4-week prospective, open-label trial, in which patients (n = 20) assumed daily Feru-guard® (3.0 g/day), was designed.
*toxicity↓, Salau et al. [130] did not find signs of toxicity of ferulic acid in hippocampal neuronal cell lines HT22 cells, thus concluding that the substance seems to be safe in healthy brain cells
*antiOx↑, Silymarin (SM) is a well-known antioxidant, anti-inflammatory and anti-cancer compound extracted from the milk thistle.
*Inflam↓,
AntiCan↑,
*ROS↓, SM could reduce ROS and MDA levels and increase GSH levels in AA-induced PC12 cells.
*MDA↓,
*GSH↓,
*NRF2↑, SM could activate Nrf2 signalling and increase the expression of Nrf2, Gpx, GCLC and GCLM in AA-treated PC12 cells.
*GPx↑,
*GCLC↑,
*GCLM↑,
*antiOx↑, antioxidant capabilities of shikonin and its ability to protect human keratinocytes from oxidative stress induced by fine particulate matter
*ROS↓, 3 µM was nontoxic to human keratinocytes and effectively scavenged reactive oxygen species (ROS) while increasing the production of reduced glutathione (GSH).
*GSH↑,
*GCLC↑, Shikonin increased the expression of GCLC and GSS via AKT and NRF2 activation
*GSS↑,
*Akt↑,
*NRF2↑,
*COX2↓, Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2)
*NF-kB↓, TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin
*p‑Akt↓, Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase,
*p‑cJun↓,
*p‑p38↓,
*HO-1↑, Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin
*NADPH↑,
*GSTA1↑,
*antiOx↑, provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.
*Inflam↓,
*NQO1↑, Topical application of TQ (5 lmol) significantly increased the expression of HO-1 (Fig. 4A), NQO1 (Fig. 4B), GCL (Fig. 4C) and GST (Fig. 4D) in mouse epidermal tissue
*GCLC↑,
*GSTA1↑,
Showing Research Papers: 1 to 7 of 7
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
Ferroptosis↑, 1, GCLC↑, 2, GCLM↑, 1, HO-1↑, 1, NQO1↑, 1, NRF2↑, 1,
Metal & Cofactor Biology ⓘ
FTL↑, 1, STEAP3↑, 1,
Core Metabolism/Glycolysis ⓘ
ACSL5↑, 2, SAT1↑, 1,
Cell Death ⓘ
Casp9↑, 1, Ferroptosis↑, 1,
DNA Damage & Repair ⓘ
TP53↑, 1,
Proliferation, Differentiation & Cell State ⓘ
Wnt/(β-catenin)↓, 1,
Migration ⓘ
TumCP↓, 1,
Drug Metabolism & Resistance ⓘ
ChemoSen↑, 1, selectivity↑, 1,
Clinical Biomarkers ⓘ
TP53↑, 1,
Functional Outcomes ⓘ
AntiCan↑, 1,
Total Targets: 19
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 5, ARE↑, 1, Bil↑, 2, Catalase↑, 1, Fenton↓, 2, GCLC↑, 5, GCLM↑, 3, GPx↑, 1, GSH↓, 1, GSH↑, 1, GSS↑, 1, GSTA1↑, 2, HO-1↑, 3, lipid-P↓, 3, MDA↓, 3, NQO1↑, 3, NRF2↑, 4, ROS↓, 4, SOD↑, 2,
Metal & Cofactor Biology ⓘ
IronCh↑, 2,
Core Metabolism/Glycolysis ⓘ
NADPH↑, 1, PPARγ↑, 2,
Cell Death ⓘ
Akt↑, 1, p‑Akt↓, 1, iNOS↓, 2, JNK↓, 1, p‑MAPK?, 1, p‑MAPK↓, 1, p38↓, 1, p‑p38↓, 1,
Transcription & Epigenetics ⓘ
p‑cJun↓, 1,
Migration ⓘ
Ca+2↓, 2, VCAM-1↓, 2,
Immune & Inflammatory Signaling ⓘ
COX2↓, 3, ICAM-1↓, 2, IL1β↓, 2, IL6↓, 1, IL8↓, 1, Inflam↓, 4, NF-kB↓, 3, PGE2↓, 2, TLR4↓, 1, TNF-α↓, 2,
Synaptic & Neurotransmission ⓘ
BDNF↑, 1, ChAT↑, 1,
Protein Aggregation ⓘ
Aβ↓, 2, NLRP3↓, 2,
Drug Metabolism & Resistance ⓘ
Dose↝, 1, Half-Life↝, 1,
Clinical Biomarkers ⓘ
Bil↑, 2, GutMicro↑, 2, IL6↓, 1,
Functional Outcomes ⓘ
cognitive↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 2, radioP↑, 1, RenoP↑, 1, toxicity↓, 1,
Total Targets: 59
Scientific Paper Hit Count for: GCLC, Glutamate-Cysteine Ligase, Catalytic Subunit
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#:966 State#:% Dir#:2
wNotes=on sortOrder:rid,rpid
Home Page