Thymoquinone / ERK 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)


ERK, ERK signaling: Click to Expand ⟱
Source:
Type:
MAPK3 (ERK1)
ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.
The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior

EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.
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↓,
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↓,
3423- TQ,    Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics
- Review, Var, NA
AntiCan↑, Inflam↓, hepatoP↑, RenoP↑, BAX↑, Bak↑, Bcl-2↓, Bcl-xL↓, ROS↑, P53↑, PTEN↑, P21↑, p27↑, BRCA1↑, PI3K↓, Akt↓, MAPK↓, ERK↓, p‑ERK↓, MMPs↓, FAK↓, Twist↓, Zeb1↓, EMT↓, TumMeta↓, angioG↓, VEGF↓, HDAC↓, Maspin↑, SIRT1↑, DNMT1↓, DNMT3A↓, HDAC1↓, HDAC4↓,
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↑,
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↓,
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↑,

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 ⓘ

HO-1↑, 1,   ROS↑, 4,   ROS⇅, 3,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   MEK↓, 1,   MMP↓, 1,   Raf↓, 1,   XIAP↓, 4,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 2,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 6,   p‑Akt↓, 2,   Apoptosis↑, 3,   Bak↑, 1,   BAX↑, 3,   Bcl-2↓, 6,   Bcl-2↑, 1,   Bcl-xL↓, 1,   BID↓, 1,   Casp↑, 1,   Casp3↑, 2,   Casp7↑, 1,   Casp8↑, 1,   Casp9↑, 2,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 1,   iNOS↓, 1,   JNK↑, 2,   MAPK↓, 2,   MAPK↑, 1,   p‑MAPK↑, 1,   Mcl-1↓, 1,   Myc↓, 1,   p27↑, 3,   p38↑, 2,   p‑p38↑, 1,   survivin↓, 2,   Telomerase↓, 1,   TRAIL↑, 1,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,  

Protein Folding & ER Stress ⓘ

eIF2α↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   CYP1B1↑, 1,   DNAdam↑, 1,   DNMT1↓, 2,   DNMT3A↓, 1,   p16↑, 1,   P53↑, 3,   cl‑PARP↑, 2,   PCNA↓, 1,   UHRF1↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 3,   E2Fs↓, 1,   P21↑, 3,   TumCCA↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 1,   EMT↓, 2,   ERK↓, 7,   ERK↑, 1,   p‑ERK↓, 1,   FOXO↑, 1,   GSK‐3β↓, 2,   HDAC↓, 1,   HDAC1↓, 2,   HDAC4↓, 1,   mTOR↓, 3,   p‑mTOR↓, 1,   NOTCH↓, 1,   P70S6K↓, 1,   PI3K↓, 6,   PTEN↑, 3,   RAS↓, 1,   STAT3↓, 5,   p‑STAT3↓, 1,   TumCG↓, 1,   Wnt↓, 1,  

Migration ⓘ

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

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   angioG↑, 1,   VEGF↓, 5,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCL1↓, 1,   CXCR4↓, 2,   IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL2↑, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   JAK2↓, 3,   NF-kB↓, 4,   p‑NF-kB↑, 1,   p65↓, 3,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   ChemoSen↑, 3,   eff↑, 2,   RadioS↑, 1,   selectivity↑, 2,   TET2↑, 1,  

Clinical Biomarkers ⓘ

BRCA1↑, 1,   IL6↓, 1,   Ki-67↓, 1,   Maspin↑, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoP↑, 2,   hepatoP↑, 1,   RenoP↑, 1,  
Total Targets: 146

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSTA1↑, 1,   ROS↓, 1,   SOD↑, 1,  

Migration ⓘ

MMP13↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   Inflam↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   Half-Life↝, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,  
Total Targets: 14

Scientific Paper Hit Count for: ERK, ERK signaling
7 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#:105  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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