Thymoquinone / STAT3 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↓
- 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)


STAT3, Signal transducer and activator of transcription 3: Click to Expand ⟱
Source:
Type: Oncogene
Stat3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, survival, differentiation, and immune response.
Stat3 is frequently found to be constitutively activated in many types of cancers, including breast, prostate, lung, and head and neck cancers. (associated with poor prognosis and reduced survival.)

-STAT3 is typically activated by cytokines (such as IL-6) and growth factors binding to their respective receptors.
-Activated STAT3 upregulates the expression of genes that promote cell cycle progression (e.g., cyclin D1) and anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL).
Scientific Papers found: Click to Expand⟱
3411- TQ,    Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone
- Review, Var, NA
p‑STAT3↓, cycD1/CCND1↓, JAK2↓, β-catenin/ZEB1↓, cMyc↓, MMP7↓, MET↓, p‑Akt↓, p‑mTOR↓, CXCR4↓, Bcl-2↓, BAX↑, ROS↑, Cyt‑c↑, Twist↓, Zeb1↓, E-cadherin↑, p‑p38↑, p‑MAPK↑, ERK↑, eff↑, ERK↓, TumCP↓, TumCMig↓, TumCI↓,
3412- TQ,    Thymoquinone induces oxidative stress-mediated apoptosis through downregulation of Jak2/STAT3 signaling pathway in human melanoma cells
- in-vitro, Melanoma, SK-MEL-28 - in-vivo, NA, NA
Apoptosis↑, JAK2↓, STAT3↓, cycD1/CCND1↓, survivin↓, ROS↑, eff↓,
3413- TQ,    Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src‑mediated phosphorylation of EGF receptor tyrosine kinase
- in-vitro, CRC, HCT116
tumCV↓, Apoptosis↓, BAX↑, Bcl-2↓, Casp9↑, Casp7↑, Casp3↑, cl‑PARP↑, STAT3↓, survivin↓, cMyc↓, cycD1/CCND1↓, p27↑, P21↑, EGFR↓, ROS↑,
3414- TQ,    Thymoquinone induces apoptosis through inhibition of JAK2/STAT3 signaling via production of ROS in human renal cancer Caki cells
- in-vitro, RCC, Caki-1
tumCV↓, Apoptosis↑, P53↑, BAX↑, Cyt‑c↑, cl‑Casp9↑, cl‑Casp3↑, cl‑PARP↑, Bcl-2↓, Bcl-xL↓, p‑STAT3↓, p‑JAK2↓, STAT3↓, survivin↓, cycD1/CCND1↓, ROS↑, eff↓,
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↓,
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↑,
3573- TQ,    Chronic diseases, inflammation, and spices: how are they linked?
- Review, Var, NA
NF-kB↓, XIAP↓, PI3K↓, Akt↓, STAT3↓, JAK2↓, cSrc↓, PCNA↓, MMP2↓, ERK↓, Ki-67↓, Bcl-2↓, VEGF↓, p65↓, COX2↓, MMP9↓,
3427- TQ,    Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets
ROS⇅, Fas↑, DR5↑, TRAIL↑, Casp3↑, Casp8↑, Casp9↑, P53↑, mTOR↓, Bcl-2↓, BID↓, CXCR4↓, JNK↑, p38↑, MAPK↑, LC3II↑, ATG7↑, Beclin-1↑, AMPK↑, PPARγ↑, eIF2α↓, P70S6K↓, VEGF↓, ERK↓, NF-kB↓, XIAP↓, survivin↓, p65↓, DLC1↑, FOXO↑, TET2↑, CYP1B1↑, UHRF1↓, DNMT1↓, HDAC1↓, IL2↑, IL1↓, IL6↓, IL10↓, IL12↓, TNF-α↓, iNOS↓, COX2↓, 5LO↓, AP-1↓, PI3K↓, Akt↓, cMET↓, VEGFR2↓, CXCL1↓, ITGA5↓, Wnt↓, β-catenin/ZEB1↓, GSK‐3β↓, Myc↓, cycD1/CCND1↓, N-cadherin↓, Snail↓, Slug↓, Vim↓, Twist↓, Zeb1↓, MMP2↓, MMP7↓, MMP9↓, JAK2↓, STAT3↓, NOTCH↓, cycA1/CCNA1↓, CDK2↓, CDK4↓, CDK6↓, CDC2↓, CDC25↓, Mcl-1↓, E2Fs↓, p16↑, p27↑, P21↑, ChemoSen↑,
2083- TQ,    Thymoquinone inhibits proliferation in gastric cancer via the STAT3 pathway in vivo and in vitro
- in-vitro, GC, HGC27 - in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901 - in-vivo, NA, NA
p‑STAT3↓, JAK2↓, c-Src↓, Bcl-2↓, cycD1/CCND1↓, survivin↓, VEGF↓, Casp3?, Casp7?, Casp9?, *toxicity∅, TumVol↓,
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↓,
1935- TQ,    Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis
- Review, OS, NA
Apoptosis↑, TumCCA↑, angioG↓, TumMeta↓, ROS↑, P53↑, Twist↓, E-cadherin↑, N-cadherin↓, NF-kB↓, IL8↓, XIAP↓, Bcl-2↓, STAT3↓, MAPK↓, PI3K↓, Akt↓, ERK↓, MMP2↓, MMP9↓, *ROS↓, HO-1↑, selectivity↑, TumCG↓,
2120- TQ,    STAT3">Thymoquinone induces apoptosis of human epidermoid carcinoma A431 cells through ROS-mediated suppression of STAT3
- in-vitro, Melanoma, A431
ROS↑, Apoptosis↑, P53↑, BAX↑, MDM2↓, Bcl-2↓, Bcl-xL↓, Casp9↑, Casp7↑, Casp3↑, STAT3↓, cycD1/CCND1↓, survivin↓, eff↓,
2127- TQ,    Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways
- Review, GBM, NA
chemoP↑, ChemoSen↑, BioAv↑, PTEN↑, PI3K↓, Akt↓, TumCCA↓, NF-kB↓, p‑Akt↓, p65↓, XIAP↓, Bcl-2↓, COX2↓, VEGF↓, mTOR↓, RAS↓, Raf↓, MEK↓, ERK↓, MMP2↓, MMP9↓, TumCMig↓, TumCI↓, Casp↑, cl‑PARP↑, ROS⇅, ROS↑, MMP↓, eff↑, Telomerase↓, DNAdam↑, Apoptosis↑, STAT3↓, RadioS↑,
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↑,
2108- TQ,    Anti-cancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa
- Review, Var, NA
HDAC↓, TumCCA↑, cycD1/CCND1↓, p16↑, P53↑, Bax:Bcl2↑, Bcl-xL↓, NF-kB↓, IAP1↓, IAP2↓, XIAP↓, survivin↓, COX2↓, cMyc↓, ROS↑, Casp3↑, cl‑PARP↑, Cyt‑c↑, STAT3↓,

Showing Research Papers: 1 to 15 of 15

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 15

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 2,   HO-1↑, 1,   NRF2↑, 1,   ROS↑, 11,   ROS⇅, 4,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   CDC2↓, 1,   CDC25↓, 1,   MEK↓, 1,   MMP↓, 1,   Raf↓, 1,   XIAP↓, 6,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 5,   PPARγ↓, 1,   PPARγ↑, 1,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 6,   p‑Akt↓, 3,   Apoptosis↓, 1,   Apoptosis↑, 8,   BAX↑, 6,   Bax:Bcl2↑, 1,   Bcl-2↓, 10,   Bcl-2↑, 1,   Bcl-xL↓, 5,   BID↓, 1,   Casp↑, 2,   Casp3?, 1,   Casp3↑, 6,   cl‑Casp3↑, 1,   Casp7?, 1,   Casp7↑, 4,   Casp8↑, 1,   Casp9?, 1,   Casp9↑, 5,   cl‑Casp9↑, 1,   Cyt‑c↑, 3,   DR5↑, 1,   Fas↑, 1,   IAP1↓, 2,   IAP2↓, 2,   iNOS↓, 1,   JNK↑, 2,   MAPK↓, 1,   MAPK↑, 2,   p‑MAPK↑, 1,   Mcl-1↓, 1,   MDM2↓, 1,   Myc↓, 1,   p27↑, 3,   p38↑, 2,   p‑p38↑, 1,   survivin↓, 10,   Telomerase↓, 1,   TRAIL↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,   cSrc↓, 2,  

Transcription & Epigenetics ⓘ

EZH2↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

eIF2α↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

CYP1B1↑, 1,   DNAdam↑, 1,   DNMT1↓, 2,   GADD45A↑, 1,   p16↑, 2,   P53↑, 7,   cl‑PARP↑, 6,   PCNA↓, 1,   UHRF1↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 10,   E2Fs↓, 1,   P21↑, 4,   TumCCA↓, 1,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 1,   EMT↓, 2,   ERK↓, 6,   ERK↑, 1,   FOXO↑, 1,   GSK‐3β↓, 2,   GSK‐3β↑, 1,   HDAC↓, 3,   HDAC1↓, 2,   HDAC2↓, 1,   HDAC3↓, 1,   mTOR↓, 4,   p‑mTOR↓, 1,   NOTCH↓, 1,   P70S6K↓, 1,   PI3K↓, 6,   PI3K↑, 1,   PTEN↑, 3,   RAS↓, 1,   c-Src↓, 1,   STAT3↓, 11,   p‑STAT3↓, 5,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   DLC1↑, 1,   E-cadherin↓, 1,   E-cadherin↑, 3,   ITGA5↓, 1,   Ki-67↓, 2,   MET↓, 1,   MMP2↓, 4,   MMP7↓, 2,   MMP9↓, 6,   MMPs↓, 1,   N-cadherin↓, 3,   Slug↓, 1,   Snail↓, 1,   TumCI↓, 2,   TumCMig↓, 2,   TumCP↓, 2,   TumMeta↓, 2,   Twist↓, 5,   Vim↓, 2,   Zeb1↓, 3,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   angioG↑, 1,   EGFR↓, 1,   VEGF↓, 6,   VEGFR2↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 6,   CXCL1↓, 1,   CXCR4↓, 3,   IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL2↑, 1,   IL6↓, 1,   IL8↓, 1,   JAK2↓, 6,   p‑JAK2↓, 1,   NF-kB↓, 7,   p‑NF-kB↑, 1,   NK cell↑, 1,   p65↓, 3,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 5,   Dose↝, 1,   eff↓, 4,   eff↑, 6,   RadioS↑, 3,   selectivity↑, 4,   TET2↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   EZH2↓, 1,   IL6↓, 1,   Ki-67↓, 2,   Myc↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 2,   hepatoP↑, 1,   TumVol↓, 1,  
Total Targets: 168

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 3,   GPx↑, 3,   GSH↑, 1,   GSTA1↓, 1,   GSTA1↑, 1,   H2O2↓, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   MPO↑, 1,   ROS↓, 2,   SOD↑, 4,  

Core Metabolism/Glycolysis ⓘ

NAD↑, 1,   SIRT1↑, 1,  

Migration ⓘ

MMP13↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL1β↓, 2,   IL6↓, 1,   Inflam↓, 2,   PGE2↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

GR↑, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

CRP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   radioP↑, 1,   toxicity∅, 1,  
Total Targets: 36

Scientific Paper Hit Count for: STAT3, Signal transducer and activator of transcription 3
15 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#:373  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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