Thymoquinone / Cyt‑c 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)


Cyt‑c, cyt-c Release into Cytosol: Click to Expand ⟱
Source:
Type:
Cytochrome c
** The term "release of cytochrome c" ** an increase in level for the cytosol.
Small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. Cytochrome c is highly water-soluble, unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It also plays a major role in cell apoptosis.

The term "release of cytochrome c" refers to a critical step in the process of programmed cell death, also known as apoptosis.
In its new location—the cytosol—cytochrome c participates in the apoptotic signaling pathway by helping to form the apoptosome, which activates caspases that execute cell death.
Cytochrome c is a small protein normally located in the mitochondrial intermembrane space. Its primary role in healthy cells is to participate in the electron transport chain, a process that helps produce energy (ATP) through oxidative phosphorylation.
Mitochondrial outer membrane permeability leads to the release of cytochrome c from the mitochondria into the cytosol.
The release of cytochrome c is a pivotal event in apoptosis where cytochrome c moves from the mitochondria to the cytosol, initiating a chain reaction that leads to programmed cell death.

On the one hand, cytochrome c can promote cancer cell survival and proliferation by regulating the activity of various signaling pathways, such as the PI3K/AKT pathway. This can lead to increased cell growth and resistance to apoptosis, which are hallmarks of cancer.
On the other hand, cytochrome c can also induce apoptosis in cancer cells by interacting with other proteins, such as Apaf-1 and caspase-9. This can lead to the activation of the intrinsic apoptotic pathway, which can result in the death of cancer cells.
Overexpressed in Breast, Lung, Colon, and Prostrate.
Underexpressed in Ovarian, and Pancreatic.
Scientific Papers found: Click to Expand⟱
4774- 5-FU,  TQ,  CoQ10,    Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation
- in-vitro, CRC, NA
AntiCan↑, TumCCA↑, Apoptosis↑, eff↑, Bcl-2↓, survivin↓, P21↑, p27↑, BAX↑, Cyt‑c↑, Casp3↑, PI3K↓, Akt↓, mTOR↓, Hif1a↓, PTEN↑, AMPKα↑, PDH↑, LDHA↓, antiOx↓, ROS↑, AntiCan↑,
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↓,
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↓,
3416- TQ,    Thymoquinone induces apoptosis in bladder cancer cell via endoplasmic reticulum stress-dependent mitochondrial pathway
- in-vitro, Bladder, T24/HTB-9 - in-vitro, Bladder, 253J - in-vitro, Nor, SV-HUC-1
TumCP↓, Apoptosis↑, ER Stress↑, cl‑Casp3↑, cl‑Casp8↑, cl‑Casp7↑, cl‑PARP↑, Cyt‑c↑, PERK↑, IRE1↑, ATF6↑, p‑eIF2α↑, ATF4↑, GRP78/BiP↑, CHOP↑,
5221- TQ,    Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells
- in-vitro, AML, HL-60
chemoPv↑, Apoptosis↑, MMP↓, Casp8↑, Casp9↑, Bax:Bcl2↑, Cyt‑c↑,
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↓,
2085- TQ,    Anticancer Activities of Nigella Sativa (Black Cumin)
- Review, Var, NA
MMP↓, Casp3↑, Casp8↑, Casp9↓, cl‑PARP↑, Cyt‑c↑, Bax:Bcl2↑, NF-kB↓, IAP1↓, IAP2↓, XIAP↓, Bcl-xL↓, survivin↓, cJun↑, p38↑, Akt↑, chemoP↑, *radioP↑,
2095- TQ,    Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis
- Review, Var, NA
TumCCA↑, Apoptosis↑, ROS↑, Cyt‑c↑, Bax:Bcl2↑, Casp3↑, Casp9↑, cl‑PARP↑, P53↑, P21↑, cMyc↓, hTERT/TERT↓, cycD1/CCND1↓, CDK4↓, NF-kB↓, IAP1↓, IAP2↓, XIAP↓, Bcl-xL↓, survivin↓, COX2↓, MMP9↓, VEGF↓, eff↑,
2097- TQ,    Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human cervical carcinoma HeLa cells
- in-vitro, Cerv, HeLa
Cyt‑c↑, Bax:Bcl2↑, Casp3↑, Casp9↑, Casp8↑, cl‑PARP↑, cMyc↓, hTERT/TERT↓, cycD1/CCND1↓, CDK4↓, P53↑, P21↑, TumCP↓, Apoptosis↓, selectivity↑,
2123- TQ,    Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma
- in-vitro, lymphoma, PEL
Akt↓, ROS↑, BAX↓, MMP↓, Cyt‑c↑, eff↑, Casp9↑, Casp3↑, cl‑PARP↑, DR5↑,
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 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   ROS↑, 7,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 3,   XIAP↓, 4,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 4,   LDHA↓, 1,   PDH↑, 1,   PKM2↓, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 3,   Akt↑, 1,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 6,   BAX↓, 1,   BAX↑, 3,   Bax:Bcl2↑, 5,   Bcl-2↓, 3,   Bcl-xL↓, 4,   Casp3↑, 7,   cl‑Casp3↑, 2,   cl‑Casp7↑, 1,   Casp8↑, 3,   cl‑Casp8↑, 1,   Casp9↓, 1,   Casp9↑, 5,   cl‑Casp9↑, 1,   Cyt‑c↑, 11,   DR5↑, 1,   hTERT/TERT↓, 2,   IAP1↓, 3,   IAP2↓, 3,   JNK↑, 1,   MAPK↑, 1,   p‑MAPK↑, 1,   p27↑, 1,   p38↑, 2,   p‑p38↑, 1,   survivin↓, 6,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   H4↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ATF6↑, 1,   CHOP↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   IRE1↑, 1,   PERK↑, 1,  

DNA Damage & Repair ⓘ

p16↑, 1,   P53↑, 4,   cl‑PARP↑, 7,  

Cell Cycle & Senescence ⓘ

CDK4↓, 2,   cycD1/CCND1↓, 5,   P21↑, 3,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

CD34↓, 1,   ERK↓, 1,   ERK↑, 1,   HDAC↓, 2,   Jun↓, 1,   mTOR↓, 2,   p‑mTOR↓, 1,   NOTCH↓, 1,   PI3K↓, 2,   PTEN↑, 2,   STAT3↓, 2,   p‑STAT3↓, 2,  

Migration ⓘ

E-cadherin↑, 1,   FAK↓, 1,   Ki-67↓, 1,   MET↓, 1,   MMP7↓, 1,   MMP9↓, 2,   MUC4↓, 1,   TGF-β↓, 1,   TGF-β↑, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 4,   TumMeta↓, 1,   Twist↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↑, 1,   Hif1a↓, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   CXCR4↓, 1,   Inflam↓, 1,   JAK2↓, 1,   p‑JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 4,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↝, 1,   eff↓, 1,   eff↑, 4,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

hTERT/TERT↓, 2,   Ki-67↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   chemoP↑, 1,   chemoPv↑, 1,  
Total Targets: 106

Pathway results for Effect on Normal Cells:


Functional Outcomes ⓘ

radioP↑, 1,  
Total Targets: 1

Scientific Paper Hit Count for: Cyt‑c, cyt-c Release into Cytosol
11 Thymoquinone
1 5-fluorouracil
1 Coenzyme Q10
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#:77  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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