Thymoquinone / GPx 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↓ HO1↓(contrary), GPx">GPx↓
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, 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)


GPx, Glutathione peroxidases: Click to Expand ⟱
Source:
Type:
Glutathione peroxidases (GPXs) are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS).
Glutathione peroxidase (GPx) refers to a family of antioxidant enzymes that play a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. There are several isoforms of GPx, including GPx1, GPx2, GPx3, and GPx4, each with distinct tissue distributions and functions.
GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers.

GPx expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance.


Scientific Papers found: Click to Expand⟱
3422- TQ,    Thymoquinone, as a Novel Therapeutic Candidate of Cancers
- Review, Var, NA
selectivity↑, P53↑, PTEN↑, NF-kB↓, PPARγ↓, cMyc↓, Casp↑, *BioAv↓, BioAv↝, eff↑, survivin↓, Bcl-xL↓, Bcl-2↓, Akt↓, BAX↑, cl‑PARP↑, CXCR4↓, MMP9↓, VEGFR2↓, Ki-67↓, COX2↓, JAK2↓, cSrc↓, Apoptosis↑, p‑STAT3↓, cycD1/CCND1↓, Casp3↑, Casp7↑, Casp9↑, N-cadherin↓, Vim↓, Twist↓, E-cadherin↑, ChemoSen↑, eff↑, EMT↓, ROS↑, DNMT1↓, eff↑, EZH2↓, hepatoP↑, Zeb1↓, RadioS↑, HDAC↓, HDAC1↓, HDAC2↓, HDAC3↓, *NAD↑, *SIRT1↑, SIRT1↓, *Inflam↓, *CRP↓, *TNF-α↓, *IL6↓, *IL1β↓, *eff↑, *MDA↓, *NO↓, *GSH↑, *SOD↑, *Catalase↑, *GPx↑, PI3K↓, mTOR↓,
3398- TQ,  5-FU,    Impact of thymoquinone on the Nrf2/HO-1 and MAPK/NF-κB axis in mitigating 5-fluorouracil-induced acute kidney injury in vivo
- in-vivo, Nor, NA
*RenoP↑, *TAC↑, *ROS↓, *lipid-P↓, *p38↓, *MAPK↓, *NF-kB↓, *NRF2↑, *HO-1↑, *MDA↓, *GPx↑, *GSR↑, *Catalase↑, *BUN↓, *LDH↓, *IL1β↓,
3397- TQ,    Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
ChemoSen↑, *Half-Life↝, *BioAv↝, *antiOx↑, *Inflam↓, *hepatoP↑, TumCP↓, TumCCA↑, Apoptosis↑, angioG↑, selectivity↑, JNK↑, p38↑, p‑NF-kB↑, ERK↓, PI3K↓, PTEN↑, Akt↓, mTOR↓, EMT↓, Twist↓, E-cadherin↓, ROS⇅, *Catalase↑, *SOD↑, *GSTA1↑, *GPx↑, *PGE2↓, *IL1β↓, *COX2↓, *MMP13↓, MMPs↓, TumMeta↓, VEGF↓, STAT3↓, BAX↑, Bcl-2↑, Casp9↑, Casp7↑, Casp3↑, cl‑PARP↑, survivin↓, cMyc↓, cycD1/CCND1↓, p27↑, P21↑, GSK‐3β↓, β-catenin/ZEB1↓, chemoP↑,
5024- TQ,    Thymoquinone: A Tie-Breaker in SARS-CoV2-Infected Cancer Patients?
- Review, Covid, NA
*NRF2↑, *NF-kB↓, *Inflam↓, *ROS↓, *HO-1↑, antiOx↑, GSH↑, GSTs↑, GSR↑, SOD1↑, Catalase↑, GPx↑, p62↓, Beclin-1↑, Sepsis↓, cardioP↑, hepatoP↑, neuroP↑,
3559- TQ,    Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer’s disease
- Review, AD, NA - Review, Var, NA
*antiOx↑, *Inflam↓, *AChE↓, AntiCan↑, *cardioP↑, *RenoP↑, *neuroP↑, *hepatoP↑, TumCG↓, Apoptosis↑, PI3K↓, Akt↑, TumCCA↑, angioG↓, *NF-kB↓, *TLR2↓, *TLR4↓, *MyD88↓, *TRIF↓, *IRF3↓, *IL1β↓, *IL6↓, *IL12↓, *NRF2↑, *COX2↓, *VEGF↓, *MMP9↓, *cMyc↓, *cycD1/CCND1↓, *TumCP↓, *TumCI↓, *MDA↓, *TGF-β↓, *CRP↓, *Casp3↓, *GSH↑, *IL10↑, *iNOS↑, *lipid-P↓, *SOD↑, *H2O2↓, *ROS↓, *LDH↓, *Catalase↑, *GPx↑, *AChE↓, *cognitive↑, *MAPK↑, *JNK↑, *BAX↓, *memory↑, *Aβ↓, *MMP↑,
2134- TQ,    Modulation of Nrf2/HO1 Pathway by Thymoquinone to Exert Protection Against Diazinon-induced Myocardial Infarction in Rats
- in-vivo, Nor, NA
*ALAT↓, *AST↓, *MDA↓, *ROS↓, *GSSG↓, *GSH↑, *VitE↑, *VitC↑, *NRF2↑, *HO-1↑, *NQO1↑, *SOD↑, *cardioP↑, *GSH/GSSG↑, *GPx↑,
2087- TQ,    Nigella sativa thymoquinone-rich fraction greatly improves plasma antioxidant capacity and expression of antioxidant genes in hypercholesterolemic rats
- in-vivo, Nor, NA
*LDL↓, *SOD1↑, *Catalase↑, *GPx↑, *antiOx↑,
1937- TQ,    Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models
- NA, Nor, 3T3
*ROS↓, *antiOx↓, *BioAv↓, *BioAv↑, *NO↑, *SOD↑, *GPx↑, *Catalase↑,
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↑,

Showing Research Papers: 1 to 9 of 9

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 9

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↓, 1,   GSH↑, 1,   GSR↑, 1,   GSTs↑, 1,   NRF2↑, 1,   ROS↑, 2,   ROS⇅, 1,   SOD1↑, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   PPARγ↓, 1,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Akt↑, 1,   p‑Akt↓, 1,   Apoptosis↑, 4,   BAX↑, 2,   Bcl-2↓, 1,   Bcl-2↑, 1,   Bcl-xL↓, 1,   Casp↑, 1,   Casp3↑, 2,   Casp7↑, 2,   Casp9↑, 2,   JNK↑, 1,   MAPK↑, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 2,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   cSrc↓, 1,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNMT1↓, 1,   P53↑, 2,   cl‑PARP↑, 2,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   P21↑, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   ERK↓, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,   HDAC↓, 1,   HDAC1↓, 1,   HDAC2↓, 1,   HDAC3↓, 1,   mTOR↓, 2,   PI3K↓, 3,   PI3K↑, 1,   PTEN↑, 2,   STAT3↓, 1,   p‑STAT3↓, 2,   TumCG↓, 1,  

Migration ⓘ

E-cadherin↓, 1,   E-cadherin↑, 1,   Ki-67↓, 1,   MMP9↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   Twist↓, 2,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   angioG↑, 1,   VEGF↓, 1,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CXCR4↓, 1,   JAK2↓, 1,   NF-kB↓, 1,   p‑NF-kB↑, 1,   NK cell↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 1,   ChemoSen↑, 3,   Dose↝, 1,   eff↓, 1,   eff↑, 4,   RadioS↑, 2,   selectivity↑, 3,  

Clinical Biomarkers ⓘ

EZH2↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   chemoP↑, 1,   hepatoP↑, 2,   neuroP↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 95

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 3,   Catalase↑, 7,   GPx↑, 8,   GSH↑, 3,   GSH/GSSG↑, 1,   GSR↑, 1,   GSSG↓, 1,   GSTA1↓, 1,   GSTA1↑, 1,   H2O2↓, 2,   HO-1↑, 4,   lipid-P↓, 3,   MDA↓, 4,   NQO1↑, 1,   NRF2↑, 4,   ROS↓, 6,   SOD↑, 6,   SOD1↑, 1,   TAC↑, 1,   VitC↑, 1,   VitE↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   BUN↓, 1,   cMyc↓, 1,   LDH↓, 2,   LDL↓, 1,   NAD↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

BAX↓, 1,   Casp3↓, 1,   iNOS↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   p38↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Migration ⓘ

MMP13↓, 1,   MMP9↓, 1,   TGF-β↓, 1,   TumCI↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,   NO↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CRP↓, 2,   IL10↑, 1,   IL12↓, 1,   IL1β↓, 4,   IL6↓, 2,   Inflam↓, 4,   MyD88↓, 1,   NF-kB↓, 3,   PGE2↓, 1,   TLR2↓, 1,   TLR4↓, 1,   TNF-α↓, 1,   TRIF↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Hormonal & Nuclear Receptors ⓘ

GR↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 1,   eff↑, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   CRP↓, 2,   IL6↓, 2,   LDH↓, 2,  

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 2,   memory↑, 1,   neuroP↑, 1,   RenoP↑, 2,  

Infection & Microbiome ⓘ

IRF3↓, 1,  
Total Targets: 80

Scientific Paper Hit Count for: GPx, Glutathione peroxidases
9 Thymoquinone
1 5-fluorouracil
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#:418  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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