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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

CDK2, Cyclin-dependent kinase 2: Click to Expand ⟱

Source:

Type:

(CDK2) complex is significantly over-activated in many cancers.
CDK2 interacts with and phosphorylates proteins in pathways such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation.

Scientific Papers found: Click to Expand⟱

3408-

TQ,

Thymoquinone: A small molecule from nature with high therapeutic potential

Review,

AD,

Review,

Park,

*neuroP↑, The neuroprotective effect of TQ has been seen in various neurological disorders, including epilepsy, Parkinsonism, anxiety, depression, encephalomyelitis and Alzheimer’s disease
*hepatoP↑, Hepatoprotective activity
*cardioP↑, Cardioprotective activity
*Inflam↓, Anti-inflammatory activity
*antiOx↑, TQ is well known for its antioxidant activity
ChemoSen↑, combination of TQ with chemotherapeutic drugs shows very promising effects in different types of cancers and against different diseases in preclinical studies
eff↑, Along with curcumin and fluoxetine, TQ shows good activity as compared to alone
eff↑, Vascular endothelial growth factor (VEGF) activation lead to angiogenesis, which inhibited by a combination of resveratrol and TQ.
TumCP↓, TQ can inhibit tumor cell proliferation, inhibit carcinogen activation, arrest the cell cycle in different phases, induce apoptosis, inhibit proteasomes and inhibit angiogenesis.
TumCCA↑,
angioG↓,
cycA1↓, downregulation of cyclin A, cyclin D1, cyclin D2, cyclin E and cyclin-dependent kinases,
cycD1↓,
cycE↓,
CDK2↓,

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↓,
N-cadherin↓,
Snail↓,
Slug↓,
Vim↓,
Twist↓,
Zeb1↓,
MMP2↓,
MMP7↓,
MMP9↓,
JAK2↓, cell proliferiation
STAT3↓,
NOTCH↓,
cycA1↓,
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

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Results for Effect on Cancer/Diseased Cells:
5LO↓,1, Akt↓,1, AMPK↑,1, angioG↓,1, AP-1↓,1, ATG7↑,1, Bcl-2↓,1, Beclin-1↑,1, BID↓,1, Casp3↑,1, Casp8↑,1, Casp9↑,1, CDC2↓,1, CDC25↓,1, CDK2↓,2, CDK4↓,1, CDK6↓,1, ChemoSen↑,2, cMET↓,1, COX2↓,1, CXCL1↓,1, CXCR4↓,1, cycA1↓,2, cycD1↓,2, cycE↓,1, CYP1B1↑,1, DLC1↑,1, DNMT1↓,1, DR5↑,1, E2Fs↓,1, eff↑,2, eIF2α↓,1, ERK↓,1, Fas↑,1, FOXO↑,1, GSK‐3β↓,1, HDAC1↓,1, IL1↓,1, IL10↓,1, IL12↓,1, IL2↑,1, IL6↓,1, iNOS↓,1, ITGA5↓,1, JAK2↓,1, JNK↑,1, LC3II↑,1, MAPK↑,1, Mcl-1↓,1, MMP2↓,1, MMP7↓,1, MMP9↓,1, mTOR↓,1, Myc↓,1, N-cadherin↓,1, NF-kB↓,1, NOTCH↓,1, p16↑,1, P21↑,1, p27↑,1, p38↑,1, P53↑,1, p65↓,1, P70S6K↓,1, PI3K↓,1, PPARγ↑,1, ROS⇅,1, Slug↓,1, Snail↓,1, STAT3↓,1, survivin↓,1, TET2↑,1, TNF-α↓,1, TRAIL↑,1, TumCCA↑,1, TumCP↓,1, Twist↓,1, UHRF1↓,1, VEGF↓,1, VEGFR2↓,1, Vim↓,1, Wnt↓,1, XIAP↓,1, Zeb1↓,1, β-catenin/ZEB1↓,1,
Total Targets: 85

Results for Effect on Normal Cells:
antiOx↑,1, cardioP↑,1, hepatoP↑,1, Inflam↓,1, neuroP↑,1,
Total Targets: 5

Scientific Paper Hit Count for: CDK2, Cyclin-dependent kinase 2

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:467  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

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