Thymoquinone / Casp3 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)


Casp3, CPP32, Cysteinyl aspartate specific proteinase-3: Click to Expand ⟱
Source:
Type:
Also known as CP32.
Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death.
As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression.
Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.
Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.
On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.
Procaspase-3 is a apoptotic marker protein.
Prognostic significance:
• High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.
• Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.
Scientific Papers found: Click to Expand⟱
3409- TQ,    Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives
- in-vivo, Nor, NA
*MDA↓, *TGF-β↓, *CRP↓, *NF-kB↓, *TNF-α↓, *IL1β↓, *Casp3↓, *GSH↑, *NRF2↑, *IL10↑, *neuroP↑, *ROS↓, *Apoptosis↓, *Inflam↓,
3400- TQ,  Chemo,    Thymoquinone Ameliorates Carfilzomib-Induced Renal Impairment by Modulating Oxidative Stress Markers, Inflammatory/Apoptotic Mediators, and Augmenting Nrf2 in Rats
- in-vitro, Nor, NA
*GSH↑, *SOD↑, *lipid-P↓, *IL1β↓, *IL6↓, *TNF-α↓, *Casp3↓, *Catalase↑, *NRF2↑, *RenoP↑,
4173- TQ,    Thymoquinone Can Improve Neuronal Survival and Promote Neurogenesis in Rat Hippocampal Neurons
- in-vivo, NA, NA
*neuroP↑, *Casp3↓, *Apoptosis↓, *ERK↑, *JNK↑, *CREB↑, *iNOS↑, *BDNF∅,
3559- TQ,    Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer’s disease
- Review, AD, NA - Review, Var, NA
*antiOx↑, *Inflam↓, *AChE↓, AntiCan↑, *cardioP↑, *RenoP↑, *neuroP↑, *hepatoP↑, TumCG↓, Apoptosis↑, PI3K↓, Akt↑, TumCCA↑, angioG↓, *NF-kB↓, *TLR2↓, *TLR4↓, *MyD88↓, *TRIF↓, *IRF3↓, *IL1β↓, *IL6↓, *IL12↓, *NRF2↑, *COX2↓, *VEGF↓, *MMP9↓, *cMyc↓, *cycD1/CCND1↓, *TumCP↓, *TumCI↓, *MDA↓, *TGF-β↓, *CRP↓, *Casp3↓, *GSH↑, *IL10↑, *iNOS↑, *lipid-P↓, *SOD↑, *H2O2↓, *ROS↓, *LDH↓, *Catalase↑, *GPx↑, *AChE↓, *cognitive↑, *MAPK↑, *JNK↑, *BAX↓, *memory↑, *Aβ↓, *MMP↑,
3554- TQ,    Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons
- in-vitro, AD, NA
*GSH↑, *ROS↓, *neuroP↑, *Casp3↓, *Casp7↓, *antiOx↓, *H2O2↓,
2132- TQ,    Thymoquinone treatment modulates the Nrf2/HO-1 signaling pathway and abrogates the inflammatory response in an animal model of lung fibrosis
- in-vivo, Nor, NA
*Weight∅, *antiOx↑, *lipid-P↓, *MMP7↓, *Casp3↓, *BAX↓, *TGF-β↓, *Diff↑, *NRF2↓, *HO-1↓, *NF-kB↓, *IκB↑,
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↑,
2114- TQ,    Anti-Aging Effect of Nigella Sativa Fixed Oil on D-Galactose-Induced Aging in Mice
- in-vivo, Nor, NA
*ALAT↓, *AST↓, *lipid-P↓, *GSH↑, *Bax:Bcl2↓, *proCasp3↓, *cl‑Casp3↓, *antiOx↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Cell Death ⓘ

Akt↑, 1,   Apoptosis↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,   TumCG↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,  
Total Targets: 7

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 3,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 5,   H2O2↓, 2,   HO-1↓, 1,   HO-1↑, 1,   lipid-P↓, 4,   MDA↓, 2,   NRF2↓, 1,   NRF2↑, 4,   ROS↓, 3,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   cMyc↓, 1,   CREB↑, 1,   LDH↓, 1,  

Cell Death ⓘ

p‑Akt↑, 1,   Apoptosis↓, 2,   BAX↓, 2,   Bax:Bcl2↓, 1,   Casp3↓, 7,   cl‑Casp3↓, 1,   proCasp3↓, 1,   Casp7↓, 1,   iNOS↑, 2,   JNK↑, 2,   MAPK↑, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,   ERK↑, 1,  

Migration ⓘ

mt-ATPase↑, 1,   MMP7↓, 1,   MMP9↓, 1,   TGF-β↓, 3,   TumCI↓, 1,   TumCP↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Barriers & Transport ⓘ

MRP↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 2,   IL10↑, 2,   IL12↓, 1,   IL1β↓, 3,   IL6↓, 3,   Inflam↓, 2,   IκB↑, 1,   MyD88↓, 1,   NF-kB↓, 4,   TLR2↓, 1,   TLR4↓, 1,   TNF-α↓, 3,   TRIF↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 2,   BDNF∅, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   creat↓, 1,   CRP↓, 2,   IL6↓, 3,   LDH↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 1,   GFR↑, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 4,   RenoP↑, 3,   Weight∅, 1,  

Infection & Microbiome ⓘ

IRF3↓, 1,  
Total Targets: 73

Scientific Paper Hit Count for: Casp3, CPP32, Cysteinyl aspartate specific proteinase-3
8 Thymoquinone
1 Chemotherapy
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#:42  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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