Thymoquinone / HO-1 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)


HO-1, HMOX1: Click to Expand ⟱
Source:
Type:
(Also known as Hsp32 and HMOX1)
HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.
HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.
-widely regarded as having antioxidant and cytoprotective effects
-The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage

Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:
  Reducing oxidative stress and inflammation
  Promoting angiogenesis (the formation of new blood vessels)
  Inhibiting apoptosis (programmed cell death)
  Enhancing cell migration and invasion
When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.

A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.

-Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.
-Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.
-Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.
-EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.
-Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.
-Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.
-Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.
Scientific Papers found: Click to Expand⟱
3410- TQ,    Anti-inflammatory effects of thymoquinone and its protective effects against several diseases
- Review, Arthritis, NA
*Inflam↓, *antiOx↑, *COX2↓, *NRF2↑, *HO-1↑, *IL1β↓, *IL6↓, *TNF-α↓, *IFN-γ↓, *PGE2↓, *cardioP↑, *Catalase↑, *SOD↑, *Thiols↑, *neuroP↑, *IL12↓, *MCP1↓, *CXCc↓, *ROS↓,
3420- TQ,    Thymoquinone alleviates the accumulation of ROS and pyroptosis and promotes perforator skin flap survival through SIRT1/NF-κB pathway
- in-vitro, Nor, HUVECs - in-vitro, NA, NA
*NF-kB↓, *NLRP3↓, *angioG↑, *MMP9↑, *VEGF↑, *OS↑, *Pyro?, *ROS↓, *Apoptosis↓, *SIRT1↑, *SOD1↑, *HO-1↑, *eNOS↑, *ASC?, *Casp1↓, *IL1β↓, *IL18↓,
3405- TQ,  doxoR,    Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity and the underlying mechanism
- vitro+vivo, NA, NA
*cardioP↑, *NRF2↑, *HO-1↑, *ROS↓, *NQO1↑, *COX2↓, *NOX4↓, *GPx4↑, *FTH1↑, *p‑mTOR↓, *TGF-β↓,
3402- TQ,    Enhanced Apoptosis in Pancreatic Cancer Cells through Thymoquinone-rich Nigella sativa L. Methanol Extract: Targeting NRF2/HO-1 and TNF-α Pathways
- in-vitro, PC, PANC1 - in-vitro, PC, MIA PaCa-2
tumCV↓, NRF2↑, HO-1↑, TNF-α↓,
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↓,
2135- TQ,    Thymoquinone induces heme oxygenase-1 expression in HaCaT cells via Nrf2/ARE activation: Akt and AMPKα as upstream targets
- in-vitro, Nor, HaCaT
*HO-1↑, *NRF2↑, *e-ERK↑, *e-Akt↑, *AMPKα↑, *ROS⇅, *eff↓, *tumCV∅,
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↑,
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↑,
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↓,
2128- TQ,    Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo
- in-vivo, NA, NA
*COX2↓, *NF-kB↓, *p‑Akt↓, *p‑cJun↓, *p‑p38↓, *HO-1↑, *NADPH↑, *GSTA1↑, *antiOx↑, *Inflam↓, *NQO1↑, *GCLC↑, *GSTA1↑,
2130- TQ,    Thymoquinone Attenuates Brain Injury via an Anti-oxidative Pathway in a Status Epilepticus Rat Model
- in-vivo, Nor, NA
*eff↑, *memory↑, *NRF2↑, *HO-1↑, *SOD↑, *ROS↓,
2131- TQ,    Therapeutic impact of thymoquninone to alleviate ischemic brain injury via Nrf2/HO-1 pathway
- in-vitro, Stroke, NA - in-vivo, Nor, NA
*eff↑, *OS↑, *Inflam↓, *ROS↓, *NRF2↑, *HO-1↑,
2133- TQ,  CUR,  Cisplatin,    Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling
- in-vitro, Nor, HEK293 - in-vivo, NA, NA
*creat↓, *TNF-α↓, *IL6↓, *MRP↓, *GFR↑, *mt-ATPase↑, *p‑Akt↑, *NRF2↑, *HO-1↑, *Casp3↓, *NF-kB↓, *RenoP↑,
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 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 ⓘ

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

Mitochondria & Bioenergetics ⓘ

XIAP↓, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↑, 2,   Bcl-2↓, 1,   MAPK↓, 1,   MAPK↑, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 2,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   GSK‐3β↑, 1,   PI3K↓, 1,   PI3K↑, 1,   STAT3↓, 1,   p‑STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

E-cadherin↑, 1,   MMP2↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   TumMeta↓, 1,   Twist↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL8↓, 1,   NF-kB↓, 1,   NK cell↑, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

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

Functional Outcomes ⓘ

cardioP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 53

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 3,   GCLC↑, 1,   GPx↑, 3,   GPx4↑, 1,   GSH↑, 1,   GSH/GSSG↑, 1,   GSR↑, 1,   GSSG↓, 1,   GSTA1↓, 1,   GSTA1↑, 2,   H2O2↓, 1,   HO-1↑, 12,   lipid-P↓, 2,   MDA↓, 2,   NOX4↓, 1,   NQO1↑, 3,   NRF2↑, 9,   ROS↓, 10,   ROS⇅, 1,   SOD↑, 4,   SOD1↑, 1,   TAC↑, 1,   Thiols↑, 1,   VitC↑, 1,   VitE↑, 1,  

Metal & Cofactor Biology ⓘ

FTH1↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   BUN↓, 1,   LDH↓, 1,   NADPH↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

p‑Akt↓, 1,   p‑Akt↑, 1,   e-Akt↑, 1,   Apoptosis↓, 1,   Casp1↓, 1,   Casp3↓, 1,   MAPK↓, 1,   p38↓, 1,   p‑p38↓, 1,   Pyro?, 1,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,  

Transcription & Epigenetics ⓘ

p‑cJun↓, 1,   tumCV∅, 1,  

Proliferation, Differentiation & Cell State ⓘ

e-ERK↑, 1,   p‑mTOR↓, 1,  

Migration ⓘ

mt-ATPase↑, 1,   MMP9↑, 1,   TGF-β↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   eNOS↑, 1,   VEGF↑, 1,  

Barriers & Transport ⓘ

MRP↓, 1,  

Immune & Inflammatory Signaling ⓘ

ASC?, 1,   COX2↓, 3,   CXCc↓, 1,   IFN-γ↓, 1,   IL12↓, 1,   IL18↓, 1,   IL1β↓, 3,   IL6↓, 2,   Inflam↓, 4,   MCP1↓, 1,   NF-kB↓, 5,   PGE2↓, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

GR↑, 1,  

Drug Metabolism & Resistance ⓘ

eff↓, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

cardioP↑, 3,   GFR↑, 1,   memory↑, 1,   neuroP↑, 1,   OS↑, 2,   RenoP↑, 2,  
Total Targets: 82

Scientific Paper Hit Count for: HO-1, HMOX1
14 Thymoquinone
1 doxorubicin
1 5-fluorouracil
1 Curcumin
1 Cisplatin
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#:597  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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