| 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
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| The Warburg effect (aerobic glycolysis) is a metabolic phenotype where many cancer cells use high glycolytic flux and lactate production even when oxygen is available. Tumors often contain hypoxic regions that further drive glycolysis, but Warburg metabolism can also occur under normoxic conditions (“pseudo-hypoxia”) via oncogenic signaling and metabolic rewiring. Hypoxia-inducible factor 1 alpha (HIF-1α) is one important driver in hypoxic tumor regions. HIF-1α upregulates glycolytic genes (e.g., GLUT1, HK2, LDHA) and promotes reduced mitochondrial pyruvate oxidation in part through induction of PDK (which inhibits PDH), shifting carbon toward lactate. Warburg effect (GLUT1, LDHA, HK2, and PKM2).Classic HIF-Warburg axis: PDK1 and MCT4 (SLC16A3) (pyruvate gate + lactate export). Here are some of the key pathways and potential targets: Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓ 1.Glycolysis Inhibitors:(2-DG, 3-BP) - HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis -PFK1 Inhibitors: such as PFK-158, can reduce glycolysis -PFKFB Inhibitors: - PKM2 Inhibitors: (Shikonin) -Can reduce glycolysis - LDH Inhibitors: (Gossypol, FX11) -Reducing the conversion of pyruvate to lactate. -Inhibiting the production of ATP and NADH. - GLUT1 Inhibitors: (phloretin, WZB117) -A key transporter involved in glucose uptake. -GLUT3 Inhibitors: - PDK1 Inhibitors: (dichloroacetate) - A key enzyme involved in the regulation of glycolysis. PDK inhibitors (e.g., DCA) activate PDH and shift pyruvate into TCA/OXPHOS, reducing lactate pressure. 2.Pentose phosphate pathway: - G6PD Inhibitors: can reduce the pentose phosphate pathway 3.Hypoxia-inducible factor 1 alpha (HIF1α) pathway: - HIF1α inhibitors: (PX-478,Shikonin) -Reduce expression of glycolytic genes and inhibit cancer cell growth. 4.AMP-activated protein kinase (AMPK) pathway: -AMPK activators: (metformin,AICAR,berberine) -Can increase AMPK activity and inhibit cancer cell growth. 5.mTOR pathway: - mTOR inhibitors:(rapamycin,everolimus) -Can reduce mTOR activity and inhibit cancer cell growth. Warburg Targeting Matrix (Cancer Metabolism)
Time-Scale Flag (TSF): P / R / G
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| 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 |
| 3425- | TQ, | Advances in research on the relationship between thymoquinone and pancreatic cancer |
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#:947 State#:% Dir#:%
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