Thymoquinone / HDAC 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)


HDAC, Histone deacetylases: Click to Expand ⟱
Source:
Type:
Enzymes involved in regulating gene expression by removing acetyl groups from histones, the proteins around which DNA is wrapped.
-Many cancers exhibit altered expression levels of HDACs, which can contribute to the dysregulation of genes involved in cell growth, survival, and differentiation.
-HDACs can repress the expression of tumor suppressor genes, leading to uncontrolled cell proliferation and survival. This repression can be a key factor in the development and progression of cancer.
-HDAC inhibitors (HDACi) have been developed and are being investigated for their ability to reactivate silenced genes, induce cell cycle arrest, and promote apoptosis in cancer cells.
-HDAC1, HDAC2): Often overexpressed in various cancers, including breast, prostate, and colorectal cancers. Their overexpression is associated with poor prognosis.
-HDAC4, HDAC5): These may have both oncogenic and tumor-suppressive roles depending on the context and cancer type.
-While HDACs are not classified as traditional oncogenes, their overexpression and activity can contribute to oncogenic processes.
-HDAC inhibitor works by preventing the removal of acetyl groups from histones, thereby modulating gene expression, influencing cell behavior, and potentially reversing aberrant gene silencing seen in various diseases.
-HDAC inhibitors can help reactivate these genes, thereby inhibiting growth and inducing apoptosis in cancer cells.
Scientific Papers found: Click to Expand⟱
3407- TQ,    Thymoquinone and its pharmacological perspective: A review
- Review, NA, NA
*antiOx↑, *ROS↓, *GSTs↑, *GSR↑, *GSH↑, *RenoP↑, *IL1β↓, *TNF-α↓, *MMP13↓, *COX2↓, *PGE2↓, *radioP↑, Twist↓, EMT↓, NF-kB↓, p‑PI3K↓, p‑Akt↓, p‑GSK‐3β↓, DNMT1↓, HDAC↓,
3421- TQ,    Insights into the molecular interactions of thymoquinone with histone deacetylase: evaluation of the therapeutic intervention potential against breast cancer
- Analysis, Nor, NA - in-vivo, Nor, NA - in-vitro, BC, MCF-7 - in-vitro, Nor, HaCaT
HDAC↓, P21↑, Maspin↑, BAX↑, B2M↓, TumCCA↑, selectivity↑, *toxicity↓, TumCMig↓, TumCP↓,
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↓,
2353- TQ,    The effects of thymoquinone on pancreatic cancer: Evidence from preclinical studies
- Review, PC, NA
BioAv↝, BioAv↑, MUC4↓, PKM2↓, eff↑, TumVol↓, HDAC↓, NF-kB↓, Bcl-2↓, Bcl-xL↓, survivin↓, XIAP↓, COX2↓, PGE1↓,
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↓,
3426- TQ,    Thymoquinone-Induced Reactivation of Tumor Suppressor Genes in Cancer Cells Involves Epigenetic Mechanisms
- in-vitro, BC, MDA-MB-468 - in-vitro, AML, JK
UHRF1↓, DNMT1↓, DNMT3A↓, DNMTs↓, HDAC1↓, HDAC4↓, HDAC↓, DLC1↑, PPARγ↑, FOXO↑, TET2↑, CYP1B1↑, G9a↓,
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↓,
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↓,
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↑,
2101- TQ,    HDAC inhibition by Nigella sativa L. sprouts extract in hepatocellular carcinoma: an approach to study anti-cancer potential
- Study, HCC, NA
HDAC↓, eff↑, eff↑, AntiCan↑,
2102- TQ,    A review on therapeutic potential of Nigella sativa: A miracle herb
- Review, Var, NA
angioG↓, NF-kB↓, PPARγ↓, Bcl-2↓, Bcl-xL↓, MUC4↓, cJun↑, p38↑, P21↑, HDAC↓, *radioP↑, hepatoP↑,
2103- TQ,    Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells
- in-vitro, PC, Hs766t - in-vitro, PC, MIA PaCa-2
MCP1↓, TNF-α↓, IL1β↓, COX2↓, NF-kB↓, HDAC↓, P21↑,
2105- TQ,    Thymoquinone Promotes Pancreatic Cancer Cell Death and Reduction of Tumor Size through Combined Inhibition of Histone Deacetylation and Induction of Histone Acetylation
- in-vitro, PC, AsPC-1 - in-vitro, PC, MIA PaCa-2 - in-vitro, PC, Hs766t - in-vivo, NA, NA
tumCV↓, TumCP↓, TumCCA↑, Apoptosis↑, P53↑, Bcl-2↓, P21↑, ac‑H4↑, HDAC↓, HDAC1↓, HDAC2↓, HDAC3↓, TumVol↓,
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 14 of 14

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 14

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 2,   ROS↑, 6,   ROS⇅, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   XIAP↓, 4,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   PKM2↓, 2,   PPARγ↓, 2,   PPARγ↑, 1,   SIRT1↓, 1,   SIRT1↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis↑, 4,   Bak↑, 1,   BAX↑, 3,   Bax:Bcl2↑, 1,   Bcl-2↓, 5,   Bcl-xL↓, 6,   Casp↑, 1,   Casp3↑, 3,   Casp7↑, 1,   Casp9↑, 2,   Cyt‑c↑, 2,   IAP1↓, 2,   IAP2↓, 2,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   p27↑, 1,   p38↑, 2,   survivin↓, 5,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   EZH2↓, 1,   H4↑, 1,   ac‑H4↑, 1,   tumCV↓, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   CYP1B1↑, 1,   DNMT1↓, 4,   DNMT3A↓, 2,   DNMTs↓, 1,   G9a↓, 1,   GADD45A↑, 2,   p16↑, 1,   P53↑, 4,   cl‑PARP↑, 2,   UHRF1↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 2,   P21↑, 7,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   EMT↓, 3,   ERK↓, 1,   p‑ERK↓, 1,   FOXO↑, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 14,   HDAC1↓, 4,   HDAC2↓, 2,   HDAC3↓, 2,   HDAC4↓, 2,   Jun↓, 1,   mTOR↓, 2,   NOTCH↓, 1,   PI3K↓, 3,   p‑PI3K↓, 1,   PTEN↑, 3,   STAT3↓, 2,   p‑STAT3↓, 1,  

Migration ⓘ

DLC1↑, 1,   E-cadherin↑, 1,   FAK↓, 2,   Ki-67↓, 2,   MMP9↓, 3,   MMPs↓, 1,   MUC4↓, 3,   N-cadherin↓, 1,   TGF-β↓, 1,   TGF-β↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 4,   TumMeta↓, 2,   Twist↓, 3,   Vim↓, 1,   Zeb1↓, 2,  

Angiogenesis & Vasculature ⓘ

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

Immune & Inflammatory Signaling ⓘ

B2M↓, 1,   COX2↓, 6,   CXCR4↓, 1,   IL1β↓, 1,   Inflam↓, 2,   JAK2↓, 1,   MCP1↓, 2,   NF-kB↓, 9,   PGE1↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   BioAv↝, 2,   ChemoSen↑, 2,   Dose↝, 1,   eff↑, 6,   RadioS↑, 1,   selectivity↑, 2,   TET2↑, 1,  

Clinical Biomarkers ⓘ

B2M↓, 1,   BRCA1↑, 1,   EZH2↓, 1,   Ki-67↓, 2,   Maspin↑, 2,  

Functional Outcomes ⓘ

AntiCan↑, 2,   chemoP↑, 1,   hepatoP↑, 4,   neuroP↑, 1,   RenoP↑, 2,   TumVol↓, 2,  
Total Targets: 123

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 2,   GSR↑, 1,   GSTs↑, 1,   MDA↓, 1,   MPO↑, 1,   ROS↓, 2,   SOD↑, 2,  

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↓, 1,   PGE2↓, 1,   TNF-α↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

CRP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   neuroP↑, 1,   radioP↑, 3,   RenoP↑, 1,   toxicity↓, 1,  
Total Targets: 30

Scientific Paper Hit Count for: HDAC, Histone deacetylases
14 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#:140  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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