GSSG Cancer Research Results

GSSG, oxidized glutathione: Click to Expand ⟱
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GSSG (oxidized glutathione) is a component of the cellular redox system rather than a protein or signaling molecule produced de novo. Its levels, often evaluated along with its reduced counterpart (GSH), serve as an important index of cellular oxidative stress and redox balance.

– GSSG is generated when glutathione (GSH) neutralizes reactive oxygen species (ROS) by donating electrons; in doing so, GSH is oxidized to GSSG.

– The GSH/GSSG ratio is a sensitive marker of the intracellular redox state. Under conditions of oxidative stress (commonly observed in many cancers), this ratio often shifts toward increased GSSG.

– Elevated GSSG levels (or an increased GSSG/GSH ratio) can indicate that cancer cells are under oxidative stress, which has implications both for cancer progression and for sensitivity to certain treatments.
Scientific Papers found: Click to Expand⟱
5167- AL,    The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines
- in-vitro, Nor, 3T3 - in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, CRC, HT-29
Thiols↓, Garlic produces the thiol-reactive defence substance, allicin, upon wounding.
tumCV↓, Allicin reduced cell viability and cell proliferation in a concentration dependent manner.
TumCP↓, Allicin Inhibits Cell Proliferation
GSH↓, allicin reacts with and depletes the GSH pool.
GSSG↑, Allicin is a thiol-reagent and reacts easily with glutathione, forming S-allylmercaptoglutathione (GSSA) and leading to an increased production of GSSG
ROS↑, Allicin oxidizes thiols and causes oxidative stress in its own right.

5012- DSF,  Cu,    Advancing Cancer Therapy with Copper/Disulfiram Nanomedicines and Drug Delivery Systems
ROS↑, DSF’s anticancer mechanism is primarily due to its generating reactive oxygen species, inhibiting aldehyde dehydrogenase (ALDH) activity inhibition, and decreasing the levels of transcriptional proteins
ALDH↓,
TumCP↓, DSF also shows inhibitory effects in cancer cell proliferation, the self-renewal of cancer stem cells (CSCs), angiogenesis, drug resistance, and suppresses cancer cell metastasis.
CSCs↓,
angioG↓,
TumMeta↓,
DNAdam↑, anti-cancer mechanism of DSF/Cu (II) may be mediated by the regulation of reactive oxygen species (ROS), enzyme activity regulation, induction of DNA damage, proteasome inhibition, and transcription factors
Proteasome↓,
SOD1↓, The complex of DSF and Cu (II)has been reported to inhibit the enzyme superoxide dismutase 1 (SOD1), one of the major enzymesthat mitigates oxidative damage in melanoma cells
GSR↓, The inhibition of Glutathione reductase (GSR) inhibition by DSF disrupts glutathione GSH redox cycling, producing an accumulation of oxidized glutathione (GSSG) and a lower GSH/GSSG ratio, producing an increase in ROS level
ox-GSSG↑,
GSH/GSSG↓,
MMP↓, DSF induces the disruption of the mitochondrial membrane potential and cause apoptosis in human melanoma cell lines
Akt↓, induced the apoptosis of erbB2-positive breast cancer cells by inhibiting AKT, cyclin D1, and NFκB signaling
cycD1/CCND1↓,
NF-kB↓,
CSCs↓, In hepatocellular carcinoma, DSF decreases CSCs by inhibiting the p38 mitogen-activated protein kinase (MAPK) pathway [118].
MAPK↓,
angioG↓, Thus, the inhibition of DSF/Cu (II) in CSCs decrease angiogenesis.
DrugR↓, DSF/Cu (II) overcomes drug resistance via targeting the proteasome, epithelial–mesenchymal transition (EMT), P-gp, CSC activity
EMT↓,
Vim↓, By downregulating associated proteins such as Vimentin, DSF/Cu (II) inhibits the EMT, which consequently overcomes the paclitaxel resistance of prostate and lung cancer
BioAv↑, The use of these nanoparticle-based formulations can increase the accumulation of DSF at the target site, thereby reducing the toxic effects on healthy tissues and improving the therapeutic index.
eff↑, In clinical trials, DSF is provided orally, but Cu (II) is critical for the efficacy of DSF

1941- PL,    Piperlongumine selectively kills cancer cells and increases cisplatin antitumor activity in head and neck cancer
- in-vitro, HNSCC, NA
selectivity↑, Piperlongumine killed HNC cells regardless of p53 mutational status but spared normal cells.
eff↑, Piperlongumine increased cisplatin-induced cytotoxicity in HNC cells in a synergistic manner in vitro and in vivo.
ROS↑, Piperlongumine selectively increases ROS accumulation in HNC cells
toxicity↑, PL markedly induced death in cancer cells, while the viability of normal cells was affected only minimally at the highest concentration (15 μM) tested
GSH↓, PL decreased GSH levels and increased GSSG levels in HNC cells (Figure 2 and Supplementary Figure S1); however, PL did not increase GSSG levels in normal HOK-1 cells
GSSG↑,
*GSSG∅, however, PL did not increase GSSG levels in normal HOK-1 cells
cl‑PARP↑, PL increased the levels of PARP and PUMA proteins regardless of p53 status
PUMA↑,
GSTP1/GSTπ↓, PL regulates ROS by targeting GSTP1, a direct negative regulator of JNK [22, 23], and thereby increases JNK phosphorylation
ChemoSen↑, Piperlongumine increases the cytotoxicity of cisplatin in HNC cells in vitro and in vivo

2941- PL,    Selective killing of cancer cells by a small molecule targeting the stress response to ROS
- in-vivo, BC, MDA-MB-231 - in-vitro, OS, U2OS - in-vitro, BC, MDA-MB-453
ROS↑, . Piperlongumine increases the level of reactive oxygen species (ROS) and apoptotic cell death
Apoptosis↑,
selectivity↑, but it has little effect on either rapidly or slowly dividing primary normal cells
*ROS∅, In contrast, PL did not cause an increase in ROS levels in normal cells
GSH↓, lead to a decrease in GSH and an increase in GSSG levels in cancer cells
GSSG↑,
H2O2↑, we found that hydrogen peroxide and nitric oxide, but not superoxide anion, were among the ROS species induced by PL in cancer cells
NO↑,
Half-Life?, 0.8 hrs

2955- PL,    Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine
- in-vitro, BC, MCF-7 - in-vitro, Nor, MCF10
ROS?, Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells.
*ROS∅,
other⇅, opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1)
HO-1↑, Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells.
*HO-1↑,
NRF2↑, piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species.
Keap1↓, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1)
cl‑PARP↑, Following piperlongumine treatment, cleaved PARP levels increased in time- (Fig. 1D) and dose-dependent
selectivity↑, These data clearly show that piperlongumine has a cancer cell-selective killing effect
GSH↓, piperlongumine can selectively decrease the level of reduced GSH and increase the level of oxidized GSSG, leading to ROS accumulation and subsequent apoptosis in cancer cells
GSSG↑, we observed piperlongumine-mediated depletion of GSH, a reduction in the GSH/GSSG ratio and accumulation of intracellular ROS in MCF-7 cells but not in MCF-10A cells

2112- TQ,    Crude flavonoid extract of the medicinal herb Nigella sativa inhibits proliferation and induces apoptosis in breastcancer cells
- in-vitro, BC, MCF-7
Apoptosis↑, apoptosis, including cell shrinkage and detachment, nuclear condensation, and DNA damage, were observed after the CFENS treatments
DNAdam↑,
ROS↑, CFENS triggered ROS accumulation, GSH depletion, disruption of mitochondrial membrane potential, activation of caspases-3/7 and -9, and an increase in the Bax/Bcl-2 ratio in MCF-7 cell
GSH↓, GSH level is depleted, whereas GSSG is accumulated, resulting in a decrease in the GSH/GSSG ratio
MMP↓, ROS accumulation also induces outer mitochondrial membrane permeabilization (MMP), which leads to loss of mitochondrial membrane potential (ΔΨm)
Casp3↑,
Casp7↑,
Casp9↑,
Bax:Bcl2↑,
P53↑, CFENS induced cell cycle arrest, upregulated the expression levels of p53 and p21 proteins,
P21↑,
cycD1/CCND1↓, downregulated the expression of cyclin D1.
GSSG↑,
GSH/GSSG↓, GSH level is depleted, whereas GSSG is accumulated, resulting in a decrease in the GSH/GSSG ratio

3399- TQ,    Anticancer Effects of Thymoquinone through the Antioxidant Activity, Upregulation of Nrf2, and Downregulation of PD-L1 in Triple-Negative Breast Cancer Cells
- in-vitro, BC, MDA-MB-231 - NA, BC, MDA-MB-468
ROS↓, The results show that TQ exhibits considerable antioxidant activity and decreases the generation of H2O2,
H2O2↓,
Catalase↑, at the same time increasing catalase (CAT) activity, superoxide dismutase (SOD) enzyme, and glutathione (GSH
SOD↑,
GSH↑,
NQO1↑, TQ treatment increased the levels of the different genes involved in the oxidative stress-antioxidant defense system PRNP, NQO1, and GCLM in both cell lines
GCLM↑,
NRF2↑, Nrf2 mRNA and protein expression were also significantly increased in TQ-treated TNBC cells
PD-L1↓, increased mRNA levels while decreasing PD-L1 protein expression in both cell lines
GSSG↑, Interestingly, a significant increase in GSSG was only found at 5 µM (p < 0.01), followed by a 50% significant reduction (p > 0.001) in GSSG at 15 µM of TQ.
GPx1⇅, TQ boosted GPX1 in MDA-MB-468 cells while decreasing GPX1 in MDA-MB-231 TNBC cells
GPx4↓, mda-mb-231


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 ⓘ

Catalase↑, 1,   GCLM↑, 1,   GPx1⇅, 1,   GPx4↓, 1,   GSH↓, 5,   GSH↑, 1,   GSH/GSSG↓, 2,   GSR↓, 1,   GSSG↑, 6,   ox-GSSG↑, 1,   GSTP1/GSTπ↓, 1,   H2O2↓, 1,   H2O2↑, 1,   HO-1↑, 1,   Keap1↓, 1,   NQO1↑, 1,   NRF2↑, 2,   ROS?, 1,   ROS↓, 1,   ROS↑, 5,   SOD↑, 1,   SOD1↓, 1,   Thiols↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 2,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   Bax:Bcl2↑, 1,   Casp3↑, 1,   Casp7↑, 1,   Casp9↑, 1,   MAPK↓, 1,   Proteasome↓, 1,   PUMA↑, 1,  

Transcription & Epigenetics ⓘ

other⇅, 1,   tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 1,   cl‑PARP↑, 2,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   P21↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ALDH↓, 1,   CSCs↓, 2,   EMT↓, 1,  

Migration ⓘ

TumCP↓, 2,   TumMeta↓, 1,   Vim↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   NO↑, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,   PD-L1↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 1,   DrugR↓, 1,   eff↑, 2,   Half-Life?, 1,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

PD-L1↓, 1,  

Functional Outcomes ⓘ

toxicity↑, 1,  
Total Targets: 58

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

GSSG∅, 1,   HO-1↑, 1,   ROS∅, 2,  
Total Targets: 3

Scientific Paper Hit Count for: GSSG, oxidized glutathione
3 Piperlongumine
2 Thymoquinone
1 Allicin (mainly Garlic)
1 Disulfiram
1 Copper and Cu NanoParticles
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#:1212  State#:%  Dir#:2
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