Thymoquinone / Bcl-xL 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)


Bcl-xL, Bcl-xL: Click to Expand ⟱
Source:
Type: pro-survival proteins
The proteins of BCL-2 family are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL.
BCL-XL overexpressing cells exhibited higher tumors sphere formation capacity and expressed higher levels of some stem cell markers, supporting the concept that BCL-XL plays essential roles in the maintenance of cancer stem cell phenotype.
Scientific Papers found: Click to Expand⟱
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↓,
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↓,
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↓,
3429- TQ,    Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA hypermethylation reversal in leukemia cells
- in-vitro, AML, NA - in-vivo, NA, NA
DNMT1↓, Sp1/3/4↓, NF-kB↓, Apoptosis↑, Casp↑, Bcl-xL↓, COX2↓, iNOS↓, 5LO↓, TNF-α↓, cycD1/CCND1↓, BioAv↝, TumCG↓,
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↑,
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↓,
2120- TQ,    Thymoquinone induces apoptosis of human epidermoid carcinoma A431 cells through ROS-mediated suppression of STAT3
- in-vitro, Melanoma, A431
ROS↑, Apoptosis↑, P53↑, BAX↑, MDM2↓, Bcl-2↓, Bcl-xL↓, Casp9↑, Casp7↑, Casp3↑, STAT3↓, cycD1/CCND1↓, survivin↓, eff↓,
2121- TQ,    Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
p‑p38↑, ROS↑, TumCP↓, eff↑, XIAP↓, survivin↓, Bcl-xL↓, Bcl-2↓, Ki-67↓, *Catalase↑, *SOD↑, *GSH↑, hepatoP↑, p‑MAPK↑, JNK↓, eff↓,
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↑,
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↓, 1,   ROS↑, 10,   ROS⇅, 2,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 1,   XIAP↓, 7,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 3,   PKM2↓, 1,   PPARγ↓, 2,   SIRT1↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 4,   Akt↑, 1,   Apoptosis↑, 5,   Bak↑, 1,   BAX↑, 4,   Bax:Bcl2↑, 3,   Bcl-2↓, 9,   Bcl-xL↓, 14,   Casp↑, 2,   Casp3↑, 5,   cl‑Casp3↑, 1,   Casp7↑, 2,   Casp8↑, 1,   Casp9↓, 1,   Casp9↑, 3,   cl‑Casp9↑, 1,   Cyt‑c↑, 4,   hTERT/TERT↓, 1,   IAP1↓, 5,   IAP2↓, 4,   IAP2↑, 1,   iNOS↓, 1,   JNK↓, 1,   MAPK↓, 1,   p‑MAPK↑, 1,   Mcl-1↓, 1,   MDM2↓, 1,   p27↑, 1,   p38↑, 2,   p‑p38↑, 1,   survivin↓, 11,  

Kinase & Signal Transduction ⓘ

cSrc↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 2,   EZH2↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↑, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   DNMT1↓, 3,   DNMT3A↓, 1,   GADD45A↑, 1,   p16↑, 1,   P53↑, 8,   cl‑PARP↑, 6,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 8,   P21↑, 5,   TumCCA↑, 4,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 3,   ERK↓, 1,   p‑ERK↓, 1,   HDAC↓, 6,   HDAC1↓, 2,   HDAC2↓, 1,   HDAC3↓, 1,   HDAC4↓, 1,   miR-34a↑, 1,   mTOR↓, 2,   NOTCH↓, 1,   PI3K↓, 3,   PTEN↑, 4,   STAT3↓, 4,   p‑STAT3↓, 2,   TumCG↓, 1,  

Migration ⓘ

5LO↓, 1,   E-cadherin↑, 1,   FAK↓, 1,   Ki-67↓, 2,   MMP9↓, 3,   MMPs↓, 1,   MUC4↓, 3,   N-cadherin↓, 1,   Rac1↓, 1,   TumCI↑, 1,   TumCP↓, 1,   TumMeta↓, 2,   Twist↓, 3,   Vim↓, 1,   Zeb1↓, 2,   α-tubulin↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   VEGF↓, 4,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 7,   CXCR4↓, 1,   Inflam↓, 2,   IκB↓, 1,   JAK2↓, 1,   p‑JAK2↓, 1,   NF-kB↓, 10,   p‑p65↓, 1,   PGE1↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   BioAv↝, 3,   ChemoSen↑, 2,   Dose↝, 2,   eff↓, 3,   eff↑, 6,   RadioS↑, 2,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

AR↓, 1,   BRCA1↑, 1,   EZH2↓, 1,   hTERT/TERT↓, 1,   Ki-67↓, 2,   Maspin↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 1,   chemoP↑, 1,   chemoPv↑, 1,   hepatoP↑, 4,   RenoP↑, 1,   TumVol↓, 1,  
Total Targets: 127

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 2,   MDA↓, 1,   MPO↑, 1,   ROS↓, 1,   SOD↑, 3,  

Core Metabolism/Glycolysis ⓘ

NAD↑, 1,   SIRT1↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

CRP↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

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

Clinical Biomarkers ⓘ

CRP↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

chemoP↑, 1,   chemoPv↑, 1,   neuroP↑, 1,   radioP↑, 3,  
Total Targets: 26

Scientific Paper Hit Count for: Bcl-xL, Bcl-xL
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#:28  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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