Thymoquinone / P21 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)


P21, P21: Click to Expand ⟱
Source:
Type: Proapototic
cyclin-dependent kinase inhibitor p21 (also known as p21 WAF1/Cip1) promotes cell cycle arrest in response to many stimuli.
P21 is a cyclin-dependent kinase inhibitor that plays a crucial role in regulating the cell cycle. It is encoded by the CDKN1A gene and is a key player in the cellular response to stress, including DNA damage.
P21 is often considered a tumor suppressor because its expression is upregulated in response to p53 activation, a well-known tumor suppressor protein. When DNA damage occurs, p53 can activate the transcription of the CDKN1A gene, leading to increased levels of P21, which helps prevent the proliferation of damaged cells.
In many cancers, the p53 pathway is disrupted, leading to decreased levels of P21. p21 is a apoptotic marker protein.
Cell cycle arrest gene p21
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↑,
3413- TQ,    Thymoquinone induces apoptosis in human colon cancer HCT116 cells through inactivation of STAT3 by blocking JAK2- and Src‑mediated phosphorylation of EGF receptor tyrosine kinase
- in-vitro, CRC, HCT116
tumCV↓, Apoptosis↓, BAX↑, Bcl-2↓, Casp9↑, Casp7↑, Casp3↑, cl‑PARP↑, STAT3↓, survivin↓, cMyc↓, cycD1/CCND1↓, p27↑, P21↑, EGFR↓, ROS↑,
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↓,
3401- TQ,    Molecular mechanisms and signaling pathways of black cumin (Nigella sativa) and its active constituent, thymoquinone: a review
- Review, Var, NA
TumCP↓, *antiOx↑, *ROS↓, NRF2↑, NF-kB↓, TumCCA↑, *GABA↑, P53↑, P21↑, AMPK↑, neuroP↑, cardioP↑, hepatoP↑,
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↑,
4565- TQ,    Thymoquinone in the clinical treatment of cancer: Fact or fiction?
- Review, BC, NA
Dose↝, TumCCA↑, P21↑, cycD1/CCND1↓, TumCI↑, TumMeta↓, Bcl-2↓, Bcl-xL↓, survivin↓, PTEN↑, Akt↓, P53↑, NF-kB↓, cardioP↑, Dose↝,
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↑,
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↑,
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↑,
2122- TQ,    Review on Molecular and Therapeutic Potential of Thymoquinone in Cancer
- Review, Var, NA
ChemoSen↓, *ROS↓, *GSH↑, RenoP↑, hepatoP↑, COX2↓, NF-kB↓, chemoPv↑, neuroP↑, TumCCA↑, P21↑, p27↑, ROS↑, DNAdam↑, MUC4↓,
2124- TQ,    Thymoquinone: an emerging natural drug with a wide range of medical applications
- Review, Var, NA
hepatoP↑, Bax:Bcl2↑, cycD1/CCND1↓, P21↑, TRAIL↑, P53↑, TumCCA↑, hepatoP↑, *ALAT↓, *AST↓, *MDA↓, *GSSG↓, *COX2↓, *lipid-P↓, PPARγ↑, p38↑, ROS↑, ChemoSen↑, selectivity↑, selectivity↑, *MDA↓, *SOD↑,
2129- TQ,  doxoR,    Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells
- in-vitro, BC, MCF-7
ChemoSen↑, PTEN↑, p‑Akt↓, TumCCA↑, P53↑, P21↑, Apoptosis↑, MMP↓, Casp↑, cl‑PARP↑, Bax:Bcl2↑, eff↓, DNAdam↓, p‑γH2AX↑, ROS↑,
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↓,
2112- TQ,    Crude flavonoid extract of the medicinal herb Nigella sativa inhibits proliferation and induces apoptosis in breastcancer cells
- in-vitro, BC, MCF-7
Apoptosis↑, DNAdam↑, ROS↑, GSH↓, MMP↓, Casp3↑, Casp7↑, Casp9↑, Bax:Bcl2↑, P53↑, P21↑, cycD1/CCND1↓, GSSG↑, GSH/GSSG↓,

Showing Research Papers: 1 to 19 of 19

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 19

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   GSH↓, 3,   GSH/GSSG↓, 1,   GSSG↑, 1,   NRF2↑, 1,   ROS↑, 10,   ROS⇅, 3,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   CDC2↓, 1,   CDC25↓, 1,   MMP↓, 2,   XIAP↓, 3,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,   ATG7↑, 1,   cMyc↓, 4,   LDHA↓, 1,   PDH↑, 1,   PPARγ↓, 1,   PPARγ↑, 2,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 5,   p‑Akt↓, 1,   Apoptosis↓, 2,   Apoptosis↑, 7,   Bak↑, 1,   BAX↑, 5,   Bax:Bcl2↑, 5,   Bcl-2↓, 7,   Bcl-2↑, 1,   Bcl-xL↓, 5,   BID↓, 1,   Casp↑, 1,   Casp3↑, 7,   Casp7↑, 3,   Casp8↑, 2,   Casp9↑, 6,   Cyt‑c↑, 3,   DR5↑, 1,   Fas↑, 1,   hTERT/TERT↓, 2,   IAP1↓, 2,   IAP2↓, 2,   iNOS↓, 1,   JNK↑, 2,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↓, 1,   Myc↓, 1,   p27↑, 6,   p38↑, 4,   survivin↓, 7,   TRAIL↑, 2,  

Kinase & Signal Transduction ⓘ

AMPKα↑, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   ac‑H4↑, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

eIF2α↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   CYP1B1↑, 1,   DNAdam↓, 1,   DNAdam↑, 2,   DNMT1↓, 2,   DNMT3A↓, 1,   GADD45A↑, 2,   p16↑, 1,   P53↑, 10,   cl‑PARP↑, 5,   UHRF1↓, 1,   p‑γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 3,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 8,   E2Fs↓, 1,   P21↑, 19,   TumCCA↑, 10,  

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 1,   EMT↓, 2,   ERK↓, 3,   p‑ERK↓, 1,   FOXO↑, 1,   GSK‐3β↓, 2,   GSK‐3β↑, 1,   HDAC↓, 7,   HDAC1↓, 3,   HDAC2↓, 1,   HDAC3↓, 1,   HDAC4↓, 1,   mTOR↓, 3,   NOTCH↓, 1,   P70S6K↓, 1,   PI3K↓, 4,   PTEN↑, 5,   STAT3↓, 4,   Wnt↓, 1,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   DLC1↑, 1,   E-cadherin↓, 1,   FAK↓, 1,   ITGA5↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 3,   MMPs↓, 2,   MUC4↓, 2,   N-cadherin↓, 1,   Slug↓, 1,   Snail↓, 1,   TumCI↑, 1,   TumCMig↓, 1,   TumCP↓, 6,   TumMeta↓, 3,   Twist↓, 3,   Vim↓, 1,   Zeb1↓, 2,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   angioG↑, 1,   EGFR↓, 1,   Hif1a↓, 1,   VEGF↓, 5,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

B2M↓, 1,   COX2↓, 5,   CXCL1↓, 1,   CXCR4↓, 1,   IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL1β↓, 1,   IL2↑, 1,   IL6↓, 1,   Inflam↓, 1,   JAK2↓, 1,   MCP1↓, 1,   NF-kB↓, 9,   p‑NF-kB↑, 1,   p65↓, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↓, 1,   ChemoSen↑, 4,   Dose↝, 2,   eff↓, 1,   eff↑, 2,   selectivity↑, 5,   TET2↑, 1,  

Clinical Biomarkers ⓘ

B2M↓, 1,   BRCA1↑, 1,   EGFR↓, 1,   hTERT/TERT↓, 2,   IL6↓, 1,   Maspin↑, 2,   Myc↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   cardioP↑, 2,   chemoP↑, 2,   chemoPv↑, 1,   hepatoP↑, 7,   neuroP↑, 3,   RenoP↑, 3,   TumVol↓, 1,  
Total Targets: 166

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSSG↓, 1,   GSTA1↑, 1,   lipid-P↓, 1,   MDA↓, 2,   MPO↑, 1,   ROS↓, 3,   SOD↑, 3,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,  

Migration ⓘ

MMP13↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL1β↓, 1,   Inflam↓, 1,   PGE2↓, 1,  

Synaptic & Neurotransmission ⓘ

GABA↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   radioP↑, 2,   toxicity↓, 1,  
Total Targets: 27

Scientific Paper Hit Count for: P21, P21
19 Thymoquinone
1 5-fluorouracil
1 Coenzyme Q10
1 doxorubicin
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#:234  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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