Thymoquinone / PARP 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)


PARP, poly ADP-ribose polymerase (PARP) cleavage: Click to Expand ⟱
Source:
Type:
Poly (ADP-ribose) polymerase (PARP) cleavage is a hallmark of caspase activation. PARP (Poly (ADP-ribose) polymerase) is a family of proteins involved in a variety of cellular processes, including DNA repair, genomic stability, and programmed cell death. PARP enzymes play a crucial role in repairing single-strand breaks in DNA.
PARP has gained significant attention, particularly in the treatment of certain types of tumors, such as those with BRCA1 or BRCA2 mutations. These mutations impair the cell's ability to repair double-strand breaks in DNA through homologous recombination. Cancer cells with these mutations can become reliant on PARP for survival, making them particularly sensitive to PARP inhibitors.
PARP inhibitors, such as olaparib, rucaparib, and niraparib, have been developed as targeted therapies for cancers associated with BRCA mutations.

PARP Family:
The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes involved in a number of cellular processes, including DNA repair, genomic stability, and programmed cell death.
PARP1 is the predominant family member responsible for detecting DNA strand breaks and initiating repair processes, especially through base excision repair (BER).

PARP1 Overexpression:
In several cancer types—including breast, ovarian, prostate, and lung cancers—elevated PARP1 expression and/or activity has been reported.
High PARP1 expression in certain cancers has been associated with aggressive tumor behavior and resistance to therapies (especially those that induce DNA damage).
Increased PARP1 activity may correlate with poorer overall survival in tumors that rely on DNA repair for survival.
Scientific Papers found: Click to Expand⟱
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↑,
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↓,
3415- TQ,    The anti-neoplastic impact of thymoquinone from Nigella sativa on small cell lung cancer: In vitro and in vivo investigations
- in-vitro, Lung, H446
tumCV↓, TumCCA↑, ROS↓, CycB/CCNB1↑, CycD3↑, cycA1/CCNA1↓, cycE/CCNE↓, cDC2↓, antiOx↑, PARP↓, NRF2↓, ARE/EpRE↑, 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↑,
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↓,
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↑,
2084- TQ,    Thymoquinone, as an anticancer molecule: from basic research to clinical investigation
- Review, Var, NA
*ROS↓, *chemoPv↑, ROS↑, ROS⇅, MUC4↓, selectivity↑, AR↓, cycD1/CCND1↓, Bcl-2↓, Bcl-xL↓, survivin↓, Mcl-1↓, VEGF↓, cl‑PARP↑, ROS↑, HSP70/HSPA5↑, P53↑, miR-34a↑, Rac1↓, TumCCA↑, NOTCH↓, NF-kB↓, IκB↓, p‑p65↓, IAP1↓, IAP2↑, XIAP↓, TNF-α↓, COX2↓, Inflam↓, α-tubulin↓, Twist↓, EMT↓, mTOR↓, PI3K↓, Akt↓, BioAv↓, ChemoSen↑, BioAv↑, PTEN↑, chemoPv↑, RadioS↑, *Half-Life↝, *BioAv↝,
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↑,
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↑,
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↑,
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 ⓘ

antiOx↑, 1,   ARE/EpRE↑, 1,   NRF2↓, 1,   ROS↓, 1,   ROS↑, 10,   ROS⇅, 3,  

Mitochondria & Bioenergetics ⓘ

MEK↓, 1,   MMP↓, 4,   Raf↓, 1,   XIAP↓, 5,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 6,   PPARγ↓, 1,   SIRT1↓, 1,  

Cell Death ⓘ

Akt↓, 5,   Akt↑, 1,   p‑Akt↓, 2,   Apoptosis↓, 2,   Apoptosis↑, 7,   BAX↓, 1,   BAX↑, 4,   Bax:Bcl2↑, 5,   Bcl-2↓, 5,   Bcl-2↑, 1,   Bcl-xL↓, 6,   Casp↑, 3,   Casp3↑, 8,   cl‑Casp3↑, 2,   Casp7↑, 3,   cl‑Casp7↑, 1,   Casp8↑, 2,   cl‑Casp8↑, 1,   Casp9↓, 1,   Casp9↑, 6,   cl‑Casp9↑, 1,   Cyt‑c↑, 7,   DR5↑, 1,   hTERT/TERT↓, 2,   IAP1↓, 4,   IAP2↓, 3,   IAP2↑, 1,   JNK↑, 1,   Mcl-1↓, 1,   p27↑, 2,   p38↑, 2,   survivin↓, 8,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   EZH2↓, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

ATF6↑, 1,   CHOP↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   HSP70/HSPA5↑, 1,   IRE1↑, 1,   PERK↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   DNAdam↑, 1,   DNMT1↓, 1,   p16↑, 1,   P53↑, 7,   PARP↓, 1,   cl‑PARP↑, 13,   p‑γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 2,   cycA1/CCNA1↓, 1,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 8,   CycD3↑, 1,   cycE/CCNE↓, 1,   P21↑, 5,   TumCCA↓, 1,   TumCCA↑, 6,  

Proliferation, Differentiation & Cell State ⓘ

cDC2↓, 1,   EMT↓, 3,   ERK↓, 2,   GSK‐3β↓, 1,   HDAC↓, 2,   HDAC1↓, 1,   HDAC2↓, 1,   HDAC3↓, 1,   miR-34a↑, 1,   mTOR↓, 4,   NOTCH↓, 1,   PI3K↓, 4,   PTEN↑, 5,   RAS↓, 1,   STAT3↓, 5,   p‑STAT3↓, 2,  

Migration ⓘ

E-cadherin↓, 1,   E-cadherin↑, 1,   Ki-67↓, 1,   MMP2↓, 1,   MMP9↓, 3,   MMPs↓, 1,   MUC4↓, 1,   N-cadherin↓, 1,   Rac1↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 3,   TumMeta↓, 1,   Twist↓, 3,   Vim↓, 1,   Zeb1↓, 1,   α-tubulin↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↑, 1,   ATF4↑, 1,   EGFR↓, 1,   VEGF↓, 4,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 5,   CXCR4↓, 1,   Inflam↓, 1,   IκB↓, 1,   JAK2↓, 1,   p‑JAK2↓, 1,   NF-kB↓, 6,   p‑NF-kB↑, 1,   p65↓, 1,   p‑p65↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 1,   ChemoSen↑, 5,   eff↓, 2,   eff↑, 7,   RadioS↑, 3,   selectivity↑, 4,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 1,   EZH2↓, 1,   hTERT/TERT↓, 2,   Ki-67↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 3,   chemoPv↑, 1,   hepatoP↑, 1,  
Total Targets: 142

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 2,   GPx↑, 2,   GSH↑, 1,   GSTA1↑, 1,   MDA↓, 1,   ROS↓, 1,   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↓, 2,   PGE2↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 2,   eff↑, 1,   Half-Life↝, 2,  

Clinical Biomarkers ⓘ

CRP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoPv↑, 1,   hepatoP↑, 1,   radioP↑, 1,  
Total Targets: 28

Scientific Paper Hit Count for: PARP, poly ADP-ribose polymerase (PARP) cleavage
14 Thymoquinone
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#:239  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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