condition found tbRes List
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


β-catenin/ZEB1, β-catenin/ZEB1: Click to Expand ⟱
Source: HalifaxProj (inactivate)
Type:
β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression.
β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton.
Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype.

(MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
Scientific Papers found: Click to Expand⟱
3411- TQ,    Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone
- Review, Var, NA
p‑STAT3↓, Thymoquinone inhibited the JAK2-mediated phosphorylation of STAT3 on the 727th serine residue in SK-MEL-28 cells
cycD1↓, levels of cyclin D1, D2, and D3 were reported to be reduced in STAT3-depleted SK-MEL-28 cells
JAK2↓, The JAK2/STAT3 pathway is inactivated by thymoquinone in B16-F10 melanoma cells
β-catenin/ZEB1↓, Levels of β-catenin and Wnt/β-catenin target genes, such as c-Myc, matrix metalloproteinase-7, and Met, were found to be reduced in thymoquinone-treated bladder cancer cells.
cMyc↓,
MMP7↓,
MET↓,
p‑Akt↓, Thymoquinone dose-dependently reduced the levels of p-AKT (threonine-308), p-AKT (serine-473), p-mTOR1, and p-mTOR2 in gastric cancer cells.
p‑mTOR↓,
CXCR4↓, Thymoquinone decreased the surface expression of CXCR4 on multiple myeloma cells
Bcl-2↓, Thymoquinone time-dependently decreased BCL-2 levels and simultaneously enhanced BAX levels
BAX↑,
ROS↑, Thymoquinone-mediated ROS accumulation triggered conformational changes in BAX that sequentially resulted in the activation of the mitochondrial apoptotic pathway
Cyt‑c↑, Thymoquinone effectively increased the release of cytochrome c into the cytosol
Twist↓, Thymoquinone downregulated TWIST1 and ZEB1 and simultaneously upregulated E-cadherin in SiHa and CaSki cell lines [82].
Zeb1↓,
E-cadherin↑,
p‑p38↑, Thymoquinone-induced ROS enhanced the phosphorylation of p38-MAPK in MCF-7 cells.
p‑MAPK↑,
ERK↑, The thymoquinone-induced activation of ERK1/2
eff↑, FR180204 (ERK inhibitor) significantly reduced the viability of thymoquinone and docetaxel-treated cancer cells [
ERK↓, Thymoquinone inhibited the proliferation, migration, and invasion of A549 cells by inactivating the ERK1/2 signaling cascade
TumCP↓,
TumCMig↓,
TumCI↓,

3397- TQ,    Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
ChemoSen↑, TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development.
*Half-Life↝, These parameters remained associated with an elimination half-life (t1/2) of 63.43 ± 10.69 and 274.61 ± 8.48 min for intravenous and oral administration, respectively
*BioAv↝, TQ is characterized by slow absorption, rapid metabolism, rapid elimination and low physicochemical stability, which limits its pharmaceutical applications
*antiOx↑, Biologically active compounds from Nigella sativa have been shown to have antioxidant, antimicrobial, anti-inflammatory, antidiabetic, hepatoprotective, antiproliferative, proapoptotic, antiepileptic and immunomodulatory activities,
*Inflam↓,
*hepatoP↑,
TumCP↓, TQ exerts tumorigenic effects in a variety of ways, including modulation of the epigenetic machinery and effects on proliferation, the cell cycle, apoptosis, angiogenesis, carcinogenesis and metastasis
TumCCA↑,
Apoptosis↑,
angioG↑,
selectivity↑, TQ has low toxicity to normal cells, as confirmed by several studies, including studies on normal mouse kidney cells, normal human lung fibroblasts and normal human intestinal cells.
JNK↑, activation of c-Jun N-terminal kinases (JNK) and p38, as well as the phosphorylation of nuclear factor-?B (NF-?B) and the reduction of extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K) activi
p38↑,
p‑NF-kB↑,
ERK↓,
PI3K↓,
PTEN↑, showing higher expression of p21/p27/PTEN/BAX/Cyto-C/Casp-3
Akt↓, TQ has also been shown to downregulate the PI3K/PTEN/Akt/mTOR and WNT/?-catenin pathways, which are critical for tumorigenesis
mTOR↓,
EMT↓, downregulating the epithelial to mesenchymal transition (EMT) transcription factors twist-related protein 1 (TWIST1) and E-cadherin
Twist↓,
E-cadherin↓,
ROS⇅, TQ has been shown to act as an antioxidant at low concentrations. Higher concentrations, however, induce apoptosis of cancer cells through the induction of oxidative stress
*Catalase↑, Thymoquinone upregulates the expression of genes encoding specific enzymes, such as catalase, superoxide dismutase, glutathione reductase, glutathione S-transferase and glutathione peroxidase, whose role is to protect against reactive oxygen species
*SOD↑,
*GSTA1↑,
*GPx↑,
*PGE2↓, TQ has the ability to downregulate NF-?B, interleukin-1?, tumor necrosis factor alpha, cyclooxygenase-2 (COX-2,) matrix metalloproteinase 13 (MMP-13), prostaglandin E2 (PGE2), the interferon regulatory factor, which are associated with inflammation a
*IL1β↓,
*COX2↓,
*MMP13↓,
MMPs↓, Figure 2
TumMeta↓,
VEGF↓,
STAT3↓, TQ affects the induction of apoptosis in cancer cells by blocking the signal transducer and activator of transcription 3 (STAT3) signaling
BAX↑, upregulation of Bax and inhibition of Bcl-2 and B-cell lymphoma-extra large (Bcl-xl) expression, as well as activated caspase-9, -7 and -3, and induced cleavage of poly (ADP-ribose) polymerase (PARP).
Bcl-2↑,
Casp9↑,
Casp7↑,
Casp3↑,
cl‑PARP↑,
survivin↓, TQ also attenuated the expression of STAT3 target gene products, such as survivin, c-Myc and cyclin-D1, -D2, and enhanced the expression of cell cycle inhibitory proteins p27 and p21
cMyc↓,
cycD1↓,
p27↑,
P21↑,
GSK‐3β↓, TQ reduces the levels of p-PI3K, p-Akt, p-glycogen synthase kinase 3 (p-GSK3?) and ?-catenin, thereby inhibiting downstream COX-2 expression, which in turn leads to a reduction in PGE2
β-catenin/ZEB1↓,
chemoP↑, results support the potential use of thymoquinone in colorectal cancer chemoprevention, as TQ is effective in protecting and treating the DMH-initiated early phase of colorectal cancer.

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

1019- TQ,    Thymoquinone suppresses migration of LoVo human colon cancer cells by reducing prostaglandin E2 induced COX-2 activation
- vitro+vivo, CRC, LoVo
TumCP↓, 20 μmol/L TQ significantly reduced human LoVo colon cancer cell proliferation
p‑PI3K↓,
p‑Akt↓,
p‑GSK‐3β↓,
β-catenin/ZEB1↓,
COX2↓,
PGE2↓,
EP2↓,
EP4↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Results for Effect on Cancer/Diseased Cells:
5LO↓,1,   Akt↓,2,   p‑Akt↓,2,   AMPK↑,1,   angioG↑,1,   AP-1↓,1,   Apoptosis↑,1,   ATG7↑,1,   BAX↑,2,   Bcl-2↓,2,   Bcl-2↑,1,   Beclin-1↑,1,   BID↓,1,   Casp3↑,2,   Casp7↑,1,   Casp8↑,1,   Casp9↑,2,   CDC2↓,1,   CDC25↓,1,   CDK2↓,1,   CDK4↓,1,   CDK6↓,1,   chemoP↑,1,   ChemoSen↑,2,   cMET↓,1,   cMyc↓,2,   COX2↓,2,   CXCL1↓,1,   CXCR4↓,2,   cycA1↓,1,   cycD1↓,3,   CYP1B1↑,1,   Cyt‑c↑,1,   DLC1↑,1,   DNMT1↓,1,   DR5↑,1,   E-cadherin↓,1,   E-cadherin↑,1,   E2Fs↓,1,   eff↑,1,   eIF2α↓,1,   EMT↓,1,   EP2↓,1,   EP4↓,1,   ERK↓,3,   ERK↑,1,   Fas↑,1,   FOXO↑,1,   GSK‐3β↓,2,   p‑GSK‐3β↓,1,   HDAC1↓,1,   IL1↓,1,   IL10↓,1,   IL12↓,1,   IL2↑,1,   IL6↓,1,   iNOS↓,1,   ITGA5↓,1,   JAK2↓,2,   JNK↑,2,   LC3II↑,1,   MAPK↑,1,   p‑MAPK↑,1,   Mcl-1↓,1,   MET↓,1,   MMP2↓,1,   MMP7↓,2,   MMP9↓,1,   MMPs↓,1,   mTOR↓,2,   p‑mTOR↓,1,   Myc↓,1,   N-cadherin↓,1,   NF-kB↓,1,   p‑NF-kB↑,1,   NOTCH↓,1,   p16↑,1,   P21↑,2,   p27↑,2,   p38↑,2,   p‑p38↑,1,   P53↑,1,   p65↓,1,   P70S6K↓,1,   cl‑PARP↑,1,   PGE2↓,1,   PI3K↓,2,   p‑PI3K↓,1,   PPARγ↑,1,   PTEN↑,1,   ROS↑,1,   ROS⇅,2,   selectivity↑,1,   Slug↓,1,   Snail↓,1,   STAT3↓,2,   p‑STAT3↓,1,   survivin↓,2,   TET2↑,1,   TNF-α↓,1,   TRAIL↑,1,   TumCCA↑,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,3,   TumMeta↓,1,   Twist↓,3,   UHRF1↓,1,   VEGF↓,2,   VEGFR2↓,1,   Vim↓,1,   Wnt↓,1,   XIAP↓,1,   Zeb1↓,2,   β-catenin/ZEB1↓,4,  
Total Targets: 115

Results for Effect on Normal Cells:
antiOx↑,1,   BioAv↝,1,   Catalase↑,1,   COX2↓,1,   GPx↑,1,   GSTA1↑,1,   Half-Life↝,1,   hepatoP↑,1,   IL1β↓,1,   Inflam↓,1,   MMP13↓,1,   PGE2↓,1,   SOD↑,1,  
Total Targets: 13

Scientific Paper Hit Count for: β-catenin/ZEB1, β-catenin/ZEB1
4 Thymoquinone
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:342  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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