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


Hif1a, HIF1α/HIF1a: Click to Expand ⟱
Source:
Type:
Hypoxia-Inducible-Factor 1A (HIF1A gene, HIF1α, HIF-1α protein product)
-Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells
-HIF1A induces the expression of vascular endothelial growth factor (VEGF)
-High HIF-1α expression is associated with Poor prognosis
-Low HIF-1α expression is associated with Better prognosis

-Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.
-Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis

Key mediators of aerobic glycolysis regulated by HIF-1α.
-GLUT-1 → regulation of the flux of glucose into cells.
-HK2 → catalysis of the first step of glucose metabolism.
-PKM2 → regulation of rate-limiting step of glycolysis.
-Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.
-LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;

HIF-1α Inhibitors:
-Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).
-Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.
-EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.
-Emodin: reduce HIF-1α expression. (under hypoxia).
-Apigenin: inhibit HIF-1α accumulation.
Scientific Papers found: Click to Expand⟱
2139- TQ,    Thymoquinone regulates microglial M1/M2 polarization after cerebral ischemia-reperfusion injury via the TLR4 signaling pathway
- in-vivo, Nor, NA
*TLR4↓, TQ inhibits the TLR4 / NF-κB pathway to regulate microglia polarization.
*NF-kB↓,
*Inflam↓, TQ attenuates inflammation in brain I/R by affecting microglia polarization.
*Hif1a↑, TQ can activate Hif-1α to counter-regulate the TLR4 / NF-κB pathway.
*motorD↑, TQ could improve the motor deficits caused by I/R.

2138- TQ,    Thymoquinone has a synergistic effect with PHD inhibitors to ameliorate ischemic brain damage in mice
- in-vivo, Nor, NA
*Hif1a↑, TQ can activate the HIF-1α pathway and its downstream genes such as VEGF, TrkB, and PI3K, which in turn enhance angiogenesis and neurogenesis.
*VEGF↑,
*TrkB↑,
*PI3K↑,
*angioG↑, which in turn enhance angiogenesis and neurogenesis.
*neuroG↑,
*motorD↑, TQ has the same effect as DMOG to activate HIF-1 α and can improve motor dysfunction after ischemic stroke

3431- TQ,    PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW48
Glycolysis↓, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines.
Warburg↓,
HK2↓, was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2),
ATP↓, such reduction in glucose fermentation capacity also led to a significant reduction in overall ATP production as well as maintaining the redox state (NADPH production) of these cells
NADPH↓, showed a significant reduction in glucose fermentation, ATP and NADPH production rates
PI3K↓, reduction in HK2 levels upon TQ treatment coincided with significant inhibition in PI3K-AKT activation
Akt↓,
TumCP↓, Thymoquinone Inhibits Cell Migration and Invasion via Modulating Glucose Metabolic Reprogramming
E-cadherin↑, TQ was able to induce E-cadherin while inhibiting N-cadherin expression
N-cadherin↓,
Hif1a↓, TQ is reported to induce cell death in renal cell carcinoma [81] and pancreatic cancers [82] via inhibiting HIF1α and pyruvate kinase M2 (PKM2)-mediated glycolysis
PKM2↓,
GlucoseCon↓, TQ treatment inhibited the glucose uptake and subsequent lactate production in HCT116 and SW480 cells
lactateProd↓,
EMT↓, TQ inhibits cell proliferation, clonogenicity and epithelial-mesenchymal transition (EMT) in CRC cells (HCT116 and SW480)

962- TQ,    Thymoquinone affects hypoxia-inducible factor-1α expression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways
- in-vitro, PC, PANC1 - in-vitro, Nor, hTERT-HPNE - in-vitro, PC, AsPC-1 - in-vitro, PC, Bxpc-3
TumCMig↓,
TumCI↓,
Apoptosis↑, no significant effects on hTERT-HPNE cells (normal cells) ****
Hif1a↓, TQ significantly reduced the mRNA and protein expression levels of HIF-1α in PANC-1, AsPC-1, and BxPC-3 cells.
PI3k/Akt/mTOR↓,
TumCCA↑, possible mechanism of TQ's influence on PC cell cycle was that TQ inhibited the proliferation of cancer cells (reducing the proportion of S phase) and damaged the DNA of cancer cells (increasing the proportion of G2/M phase). No effect on normal cell
*toxicity↓, TQ had no significant effect on the viability of hTERT-HPNE cells
*TumCI∅, no significant difference in the invasion ability of the hTERT-HPNE cells
*TumCMig∅, no significant effect on the migration and invasion of normal pancreatic ductal epithelial cells.

2125- TQ,    Thymoquinone Selectively Kills Hypoxic Renal Cancer Cells by Suppressing HIF-1α-Mediated Glycolysis
- in-vitro, RCC, RCC4 - in-vitro, RCC, Caki-1
Hif1a↓, TQ reduced HIF-1α protein levels in renal cancer cells. In addition, decreased HIF-1α levels in both cytoplasm and nucleus after treatment with 10 μM of TQ were observed in Caki-1 cells
eff↝, suggesting that suppression of HIF-1α by TQ may be connected to Hsp90-mediated HIF-1α stabilization
uPAR↓, significantly downregulated the hypoxia-induced tumor promoting HIF-1α target genes, such as FN1, LOXL2, uPAR, VEGF, CA-IX, PDK1, GLUT1, and LDHA, in TQ-treated Caki-1
VEGF↓,
CAIX↓,
PDK1↓,
GLUT1↓,
LDHA↓,
Glycolysis↓, we found that TQ significantly increases glucose levels in hypoxic Caki-1 and A498 cultured medium, indicating that hypoxia-induced anaerobic glycolysis is significantly suppressed by TQ treatment
e-lactateProd↓, Consistent with suppression of hypoxic glycolysis by TQ treatment, increased extracellular lactate levels under hypoxia were decreased in TQ-treated Caki-1 and A498 renal cancer cells
i-ATP↓, intracellular ATP levels were significantly decreased in TQ-treated Caki-1 and A498 cells under hypoxia


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   Apoptosis↑,1,   ATP↓,1,   i-ATP↓,1,   CAIX↓,1,   E-cadherin↑,1,   eff↝,1,   EMT↓,1,   GlucoseCon↓,1,   GLUT1↓,1,   Glycolysis↓,2,   Hif1a↓,3,   HK2↓,1,   lactateProd↓,1,   e-lactateProd↓,1,   LDHA↓,1,   N-cadherin↓,1,   NADPH↓,1,   PDK1↓,1,   PI3K↓,1,   PI3k/Akt/mTOR↓,1,   PKM2↓,1,   TumCCA↑,1,   TumCI↓,1,   TumCMig↓,1,   TumCP↓,1,   uPAR↓,1,   VEGF↓,1,   Warburg↓,1,  
Total Targets: 29

Results for Effect on Normal Cells:
angioG↑,1,   Hif1a↑,2,   Inflam↓,1,   motorD↑,2,   neuroG↑,1,   NF-kB↓,1,   PI3K↑,1,   TLR4↓,1,   toxicity↓,1,   TrkB↑,1,   TumCI∅,1,   TumCMig∅,1,   VEGF↑,1,  
Total Targets: 13

Scientific Paper Hit Count for: Hif1a, HIF1α/HIF1a
5 Thymoquinone
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:162  Target#:143  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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