Database Query Results : Thymoquinone, , CDK4

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)


CDK4, Cyclin-dependent kinase 4: Click to Expand ⟱
Source:
Type:
Cyclin-dependent kinase 4 (CDK4) is a key regulator of the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression and activity are often altered in various cancers, contributing to tumorigenesis.
CDK4 is frequently overexpressed in various cancers, and its expression levels can serve as a prognostic marker.
Scientific Papers found: Click to Expand⟱
3427- TQ,    Chemopreventive and Anticancer Effects of Thymoquinone: Cellular and Molecular Targets
ROS⇅, It appears that the cellular and/or physiological context(s) determines whether TQ acts as a pro-oxidant or an anti-ox- idant in vivo
Fas↑, Figure 2, cell death
DR5↑,
TRAIL↑,
Casp3↑,
Casp8↑,
Casp9↑,
P53↑,
mTOR↓,
Bcl-2↓,
BID↓,
CXCR4↓,
JNK↑,
p38↑,
MAPK↑,
LC3II↑,
ATG7↑,
Beclin-1↑,
AMPK↑,
PPARγ↑, cell survival
eIF2α↓,
P70S6K↓,
VEGF↓,
ERK↓,
NF-kB↓,
XIAP↓,
survivin↓,
p65↓,
DLC1↑, epigenetic
FOXO↑,
TET2↑,
CYP1B1↑,
UHRF1↓,
DNMT1↓,
HDAC1↓,
IL2↑, inflammation
IL1↓,
IL6↓,
IL10↓,
IL12↓,
TNF-α↓,
iNOS↓,
COX2↓,
5LO↓,
AP-1↓,
PI3K↓, invastion
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↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1/CCNA1↓,
CDK2↓,
CDK4↓,
CDK6↓,
CDC2↓,
CDC25↓,
Mcl-1↓,
E2Fs↓,
p16↑,
p27↑,
P21↑,
ChemoSen↑, Such chemo-potentiating effects of TQ in different cancer cells have been observed with 5-fluorouracil in gastric cancer and colorectal cancer models

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↑, cell cycle arrest, apoptosis induction, ROS generation
Apoptosis↑,
ROS↑,
Cyt‑c↑, release of mitochondrial cytochrome C, an increase in the Bax/Bcl-2 ratio, activations of caspases-3, -9 and -8, cleavage of PARP
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
cl‑PARP↑,
P53↑, increased expressions of p53 and p21,
P21↑,
cMyc↓, decreased expressions of oncoproteins (c-Myc), human telomerase reverse transcriptase (hTERT), cyclin D1, and cyclin-dependent kinase-4 (CDK-4).
hTERT/TERT↓,
cycD1/CCND1↓,
CDK4↓,
NF-kB↓, inhibited NF-κB activation
IAP1↓, (IAP1, IAP2, XIAP Bcl-2, Bcl-xL, and survivin), proliferative (cyclin D1, cyclooxygenase-2, and c-Myc), and angiogenic (matrix metalloproteinase-9 and vascular endothelial growth factor)
IAP2↓,
XIAP↓,
Bcl-xL↓,
survivin↓,
COX2↓,
MMP9↓,
VEGF↓,
eff↑, combination of TQ and cisplatin in the treatment of lung cancer in a mouse xenograft model showed that TQ was able to inhibit cell proliferation (nearly 90%), reduce cell viability, induce apoptosis, and reduce tumor volume and tumor weight

2097- TQ,    Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human cervical carcinoma HeLa cells
- in-vitro, Cerv, HeLa
Cyt‑c↑, release of mitochondrial cytochrome c, increase of Bax/Bcl-2 ratio, activation of caspases-3, -9 and -8 and cleavage of poly (ADP-ribose) polymerase (PARP).
Bax:Bcl2↑,
Casp3↑,
Casp9↑,
Casp8↑,
cl‑PARP↑,
cMyc↓, EENS decreased expression of oncoproteins such as c-Myc, human telomerase reverse transcriptase (hTERT), cyclin D1 and cyclin-dependent kinase-4 (CDK-4), but increased expression of tumor-suppressor proteins including p53 and p21.
hTERT/TERT↓,
cycD1/CCND1↓,
CDK4↓,
P53↑,
P21↑,
TumCP↓, EENS inhibits proliferation and induces apoptosis in HeLa cells
Apoptosis↓,
selectivity↑, On the other hand, they exerted marginal effect on the non-malignant human fibroblasts HF-5, which suggests that the EENS and AENS may selectively target cervical cancer cells but spare normal cell line.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,   ROS⇅, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 2,   PPARγ↑, 1,  

Cell Death ⓘ

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

Protein Folding & ER Stress ⓘ

eIF2α↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

CYP1B1↑, 1,   DNMT1↓, 1,   p16↑, 1,   P53↑, 3,   cl‑PARP↑, 2,   UHRF1↓, 1,  

Cell Cycle & Senescence ⓘ

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

Proliferation, Differentiation & Cell State ⓘ

cMET↓, 1,   ERK↓, 1,   FOXO↑, 1,   GSK‐3β↓, 1,   HDAC1↓, 1,   mTOR↓, 1,   NOTCH↓, 1,   P70S6K↓, 1,   PI3K↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

5LO↓, 1,   AP-1↓, 1,   DLC1↑, 1,   ITGA5↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 2,   N-cadherin↓, 1,   Slug↓, 1,   Snail↓, 1,   TumCP↓, 1,   Twist↓, 1,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 2,   VEGFR2↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCL1↓, 1,   CXCR4↓, 1,   IL1↓, 1,   IL10↓, 1,   IL12↓, 1,   IL2↑, 1,   IL6↓, 1,   JAK2↓, 1,   NF-kB↓, 2,   p65↓, 1,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   eff↑, 1,   selectivity↑, 1,   TET2↑, 1,  

Clinical Biomarkers ⓘ

hTERT/TERT↓, 2,   IL6↓, 1,   Myc↓, 1,  
Total Targets: 98

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: CDK4, Cyclin-dependent kinase 4
3 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#:894  State#:%  Dir#:%
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