Thymoquinone / GSH Cancer Research Results

TQ, Thymoquinone: Click to Expand ⟱
Features: Anti-oxidant, anti-tumor
Thymoquinone is a bioactive compound found in the seeds of Nigella sativa, commonly known as black seed or black cumin.
Pathways:
-Cell cycle arrest, apoptosis induction, ROS generation in cancer cells
-inhibit the activation of NF-κB, Suppress the PI3K/Akt signaling cascade
-Inhibit angiogenic factors such as VEGF, MMPs
-Inhibit HDACs, UHRF1, and DNMTs

-Note half-life 3-6hrs.
BioAv low oral bioavailability due to its lipophilic nature. Note refridgeration of Black seed oil improves the stability of TQ.
DIY: ~1 part lecithin : 2–3 parts black seed oil : 4–5 parts warm water. (chat ai)
Pathways:
- usually induce ROS production in Cancer cells, and lowers ROS in normal cells
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- May Low AntiOxidant defense in Cancer Cells: NRF2↓(usually contrary), GSH↓">GSH HO1↓(contrary), GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑">GSH, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, EZH2↓, P53↑, HSP↓, Sp proteins↓, TET↑
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PDKs↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Target Axis Direction Label Primary Effect Notes / Cancer Relevance Ref
1 Reactive oxygen species (ROS) ↑ ROS Driver Upstream cytotoxic trigger Primary studies show TQ rapidly increases ROS; antioxidant/ROS modulation attenuates downstream effects, supporting ROS as an initiating mechanism in multiple cancer contexts (ref)
2 Glutathione (GSH) redox buffering GSH Driver Redox-collapse amplification Same prostate cancer study reports early GSH depletion alongside ROS rise; together these form a redox “one-two punch” that helps explain selective stress in tumor cells (ref)
3 Mitochondrial integrity (ΔΨm) ↓ ΔΨm Driver Mitochondrial dysfunction (MOMP axis) Primary leukemia/cancer study reports disruption of mitochondrial membrane potential after TQ exposure (mitochondrial events central to TQ-mediated death) (ref)
4 Intrinsic apoptosis (caspase-9 → caspase-3; PARP) ↑ caspases / ↑ apoptosis Driver Execution-phase cell death Same primary paper reports activation of caspases (8/9/3) with mitochondrial involvement—core evidence for apoptosis as the major outcome pathway (ref)
5 NF-κB signaling ↓ NF-κB activity Secondary Reduced pro-survival / inflammatory transcription Colon cancer work: TQ induces cell death and chemosensitizes cells by inhibiting NF-κB signaling (explicit pathway-direction support) (ref)
6 STAT3 signaling ↓ p-STAT3 / ↓ STAT3 activation Secondary Reduced survival/proliferation signaling Gastric cancer study explicitly reports TQ suppresses constitutive STAT3 activation and related signaling readouts (ref)
7 NRF2 antioxidant-response axis (NRF2/HO-1 program) ↑ NRF2 pathway (often as stress-response) Adaptive Cellular antioxidant counter-response In TNBC context, a primary study reports TQ upregulates NRF2 (and evaluates downstream immune/checkpoint consequences), consistent with NRF2 acting as an adaptive response to redox stress (ref)
8 HIF-1α hypoxia signaling ↓ HIF-1α protein / ↓ HIF-1α program Adaptive Loss of hypoxia survival signaling Renal cancer hypoxia paper identifies TQ as suppressing HIF-1α and links this to selective killing under hypoxia (ref)
9 Glycolysis / Warburg output (hypoxia-linked) ↓ glycolysis (↓ HIF-1α–mediated glycolytic genes; ↓ glycolytic metabolism) Phenotypic Metabolic suppression In hypoxic renal cancer, TQ suppresses HIF-1α–mediated glycolysis; in CRC, TQ inhibits glycolytic metabolism alongside tumor growth limitation (ref)  |  (ref)


GSH, Glutathione: Click to Expand ⟱
Source:
Type:
Glutathione (GSH) is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress.
Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system.
cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment.
While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied.
Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy.
Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death.
Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion.
Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS).

"...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..."
"Cancer cells have a high level of GSH compared to normal cells."
"...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy."

The loss of GSH is broadly known to be directly related to the apoptosis progression.


Scientific Papers found: Click to Expand⟱
2100- TQ,    Dual properties of Nigella Sative: Anti-oxidant and Pro-oxidant
- Review, NA, NA
ROS⇅, *antiOx↑, *SOD↑, *MPO↑, *neuroP↑, *chemoP↑, *radioP↑, NF-kB↓, IAP1↓, IAP2↓, XIAP↓, Bcl-xL↓, survivin↓, COX2↓, MMP9↓, VEGF↓, ROS↑, P21↑, HDAC↓, GSH↓, GADD45A↑, AIF↑, STAT3↓,
1934- TQ,    Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species
- in-vitro, Pca, PC3 - in-vitro, Pca, C4-2B
ROS↑, GSH↓, eff↓, AR↓,
2119- TQ,    Dual properties of Nigella Sativa: anti-oxidant and pro-oxidant
- Review, Var, NA
*ROS↓, ROS↑, chemoP↑, RenoP↑, hepatoP↑, NLRP3↓, neuroP↑, NF-kB↓, P21↑, HDAC↓, Apoptosis↑, TumCP↓, GSH↓, GADD45A↑, GSK‐3β↑,
2106- TQ,    Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy
- Review, Var, NA
Apoptosis↑, TumCCA↑, ROS↑, *Catalase↑, *SOD↑, *GR↑, *GSTA1↓, *GPx↑, *H2O2↓, *ROS↓, *lipid-P↓, *HO-1↑, p‑Akt↓, AMPKα↑, NK cell↑, selectivity↑, Dose↝, eff↑, GSH↓, eff↓, P53↑, p‑STAT3↓, PI3K↑, MAPK↑, GSK‐3β↑, ChemoSen↑, RadioS↑, BioAv↓, NRF2↑,
2110- TQ,    Nigella sativa seed oil suppresses cell proliferation and induces ROS dependent mitochondrial apoptosis through p53 pathway in hepatocellular carcinoma cells
- in-vitro, HCC, HepG2 - in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Nor, HEK293
P53↑, lipid-P↑, GSH↓, ROS↑, MMP↓, BAX↑, Casp3↑, Casp9↑, Bcl-2↓, tumCV↓, selectivity↑,
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↑, DNAdam↑, ROS↑, GSH↓, MMP↓, Casp3↑, Casp7↑, Casp9↑, Bax:Bcl2↑, P53↑, P21↑, cycD1/CCND1↓, GSSG↑, GSH/GSSG↓,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

GSH↓, 6,   GSH/GSSG↓, 1,   GSSG↑, 1,   lipid-P↑, 1,   NRF2↑, 1,   ROS↑, 6,   ROS⇅, 1,  

Mitochondria & Bioenergetics

AIF↑, 1,   MMP↓, 2,   XIAP↓, 1,  

Cell Death

p‑Akt↓, 1,   Apoptosis↑, 3,   BAX↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   Casp3↑, 2,   Casp7↑, 1,   Casp9↑, 2,   IAP1↓, 1,   IAP2↓, 1,   MAPK↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction

AMPKα↑, 1,  

Transcription & Epigenetics

tumCV↓, 1,  

DNA Damage & Repair

DNAdam↑, 1,   GADD45A↑, 2,   P53↑, 3,  

Cell Cycle & Senescence

cycD1/CCND1↓, 1,   P21↑, 3,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State

GSK‐3β↑, 2,   HDAC↓, 2,   PI3K↑, 1,   STAT3↓, 1,   p‑STAT3↓, 1,  

Migration

MMP9↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature

VEGF↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 1,   NF-kB↓, 2,   NK cell↑, 1,  

Protein Aggregation

NLRP3↓, 1,  

Hormonal & Nuclear Receptors

AR↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 1,   ChemoSen↑, 1,   Dose↝, 1,   eff↓, 2,   eff↑, 1,   RadioS↑, 1,   selectivity↑, 2,  

Clinical Biomarkers

AR↓, 1,  

Functional Outcomes

chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   RenoP↑, 1,  
Total Targets: 56

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSTA1↓, 1,   H2O2↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   MPO↑, 1,   ROS↓, 2,   SOD↑, 2,  

Hormonal & Nuclear Receptors

GR↑, 1,  

Functional Outcomes

chemoP↑, 1,   neuroP↑, 1,   radioP↑, 1,  
Total Targets: 14

Scientific Paper Hit Count for: GSH, Glutathione
6 Thymoquinone
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#:162  Target#:137  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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