Thymoquinone / NOTCH 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">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)


NOTCH, : Click to Expand ⟱
Source: HalifaxProj(block) CGL-CF TCGA
Type:
Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types.; Notch hyperactivation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL).
Due to its dual roles, NOTCH signaling is being explored as a therapeutic target. Inhibitors of NOTCH signaling are being investigated in clinical trials for various cancers, particularly those with aberrant NOTCH activation.
The abnormal activation of the NOTCH pathway has been linked to increased cancer cell growth, survival, invasion, and resistance to chemotherapy and radiation therapy. On the other hand, blocking the NOTCH pathway has been shown to trigger cancer cell differentiation and cell death, and it makes them more responsive to therapy. Hence, inhibiting the NOTCH pathway has become a promising approach for treating cancer, and various NOTCH pathway inhibitors are currently under development for cancer treatment.
Scientific Papers found: Click to Expand⟱
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↑,
3425- TQ,    Advances in research on the relationship between thymoquinone and pancreatic cancer
Apoptosis↑, TumCP↓, TumCI↓, TumMeta↓, ChemoSen↑, angioG↓, Inflam↓, NF-kB↓, PI3K↓, Akt↓, TGF-β↓, Jun↓, p38↑, MAPK↑, MMP9↓, PKM2↓, ROS↑, JNK↑, MUC4↓, TGF-β↑, Dose↝, FAK↓, NOTCH↓, PTEN↑, mTOR↓, Warburg↓, XIAP↓, COX2↓, Casp9↑, Ki-67↓, CD34↓, VEGF↓, MCP1↓, survivin↓, Cyt‑c↑, Casp3↑, H4↑, HDAC↓,
2084- TQ,    Thymoquinone, as an anticancer molecule: from basic research to clinical investigation
- Review, Var, NA
*ROS↓, *chemoPv↑, ROS↑, ROS⇅, MUC4↓, selectivity↑, AR↓, cycD1/CCND1↓, Bcl-2↓, Bcl-xL↓, survivin↓, Mcl-1↓, VEGF↓, cl‑PARP↑, ROS↑, HSP70/HSPA5↑, P53↑, miR-34a↑, Rac1↓, TumCCA↑, NOTCH↓, NF-kB↓, IκB↓, p‑p65↓, IAP1↓, IAP2↑, XIAP↓, TNF-α↓, COX2↓, Inflam↓, α-tubulin↓, Twist↓, EMT↓, mTOR↓, PI3K↓, Akt↓, BioAv↓, ChemoSen↑, BioAv↑, PTEN↑, chemoPv↑, RadioS↑, *Half-Life↝, *BioAv↝,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 3,   ROS⇅, 2,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   XIAP↓, 3,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   PKM2↓, 1,   PPARγ↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 1,   Bcl-2↓, 2,   Bcl-xL↓, 1,   BID↓, 1,   Casp3↑, 2,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 1,   IAP1↓, 1,   IAP2↑, 1,   iNOS↓, 1,   JNK↑, 2,   MAPK↑, 2,   Mcl-1↓, 2,   Myc↓, 1,   p27↑, 1,   p38↑, 2,   survivin↓, 3,   TRAIL↑, 1,  

Transcription & Epigenetics ⓘ

H4↑, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↓, 1,   HSP70/HSPA5↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

CYP1B1↑, 1,   DNMT1↓, 1,   p16↑, 1,   P53↑, 2,   cl‑PARP↑, 1,   UHRF1↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 2,   E2Fs↓, 1,   P21↑, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   cMET↓, 1,   EMT↓, 1,   ERK↓, 1,   FOXO↑, 1,   GSK‐3β↓, 1,   HDAC↓, 1,   HDAC1↓, 1,   Jun↓, 1,   miR-34a↑, 1,   mTOR↓, 3,   NOTCH↓, 3,   P70S6K↓, 1,   PI3K↓, 3,   PTEN↑, 2,   STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   DLC1↑, 1,   FAK↓, 1,   ITGA5↓, 1,   Ki-67↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 2,   MUC4↓, 2,   N-cadherin↓, 1,   Rac1↓, 1,   Slug↓, 1,   Snail↓, 1,   TGF-β↓, 1,   TGF-β↑, 1,   TumCI↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   Twist↓, 2,   Vim↓, 1,   Zeb1↓, 1,   α-tubulin↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   VEGF↓, 3,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCL1↓, 1,   CXCR4↓, 1,   IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL2↑, 1,   IL6↓, 1,   Inflam↓, 2,   IκB↓, 1,   JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 3,   p65↓, 1,   p‑p65↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   ChemoSen↑, 3,   Dose↝, 1,   RadioS↑, 1,   selectivity↑, 1,   TET2↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   IL6↓, 1,   Ki-67↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 124

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

ROS↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   Half-Life↝, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,  
Total Targets: 4

Scientific Paper Hit Count for: NOTCH,
3 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#:220  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

Home Page