Quercetin / HK2 Cancer Research Results

QC, Quercetin: Click to Expand ⟱
Features:
Plant pigment (flavonoid) found in red wine, onions, green tea, apples and berries.
Quercetin is thought to contribute to anticancer effects through several mechanisms:
-Antioxidant Activity:
-Induction of Apoptosis:modify Bax:Bcl-2 ratio
-Anti-inflammatory Effects:
-Cell Cycle Arrest:
-Inhibition of Angiogenesis and Metastasis: (VEGF)

Cellular Pathways:
-PI3K/Akt/mTOR Pathway: central to cell proliferation, survival, and metabolism.
-MAPK/ERK Pathway: influencing cell proliferation, differentiation, and apoptosis.
-NF-κB Pathway: downregulate NF-κB
-JAK/STAT Pathway: interfere with the activation of STAT3
-Apoptotic Pathways: intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways

Quercetin has been used at doses around 500–1000 mg per day
Quercetin’s bioavailability from foods or standard supplements can be low.

-Note half-life 11 to 28 hours.
BioAv low 1-10%, poor water-solubility, consuming with fat may improve bioavialability. also piperine or VitC.
Pathways:
- induce ROS production in cancer cells (higher dose). Typicallys Lowers ROS in normal cells(unless it is high dose?)or depends on Redox status?. "quercetin paradox"
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓, Prx,
- Confusing info about Lowering AntiOxidant defense in Cancer Cells: NRF2↓(some contrary), TrxR↓**, SOD↓(contrary), GSH↓ Catalase↓(contrary), HO1↓(some contrary), GPx↓(some contrary)
- 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↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, FAK↓, NF-κB↓, CXCR4↓, SDF1↓, TGF-β↓, α-SMA↓, 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↓, TOP1↓, TET1,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, FGF↓, PDGF↓, EGFR↓,
- some indication of inhibiting Cancer Stem Cells : CSC↓, CK2↓, Hh↓, CD24↓, β-catenin↓, Notch2↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, α↓, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Reactive oxygen species (ROS) ↑ ROS (dose-, metal-, context-dependent) ↓ ROS Conditional Driver Biphasic redox modulation Quercetin exhibits pro-oxidant behavior in cancer cells while protecting normal cells
2 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ caspase activation ↔ preserved Driver Execution of intrinsic apoptosis Mitochondrial dysfunction is a central apoptosis route in cancer cells
3 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Driver Growth and survival inhibition AKT/mTOR suppression is a consistently reported upstream effect in cancer models
4 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Reduced survival and inflammatory transcription NF-κB inhibition contributes to chemosensitization and apoptosis susceptibility
5 MAPK signaling (JNK / p38) ↑ JNK / ↑ p38 ↔ minimal Secondary Stress-mediated apoptosis signaling MAPK activation supports apoptosis downstream of redox stress
6 Cell cycle regulation ↑ G1/S or G2/M arrest ↔ largely spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects disruption of growth signaling
7 HIF-1α hypoxia signaling ↓ HIF-1α ↔ minimal Secondary Reduced hypoxia tolerance Quercetin interferes with hypoxia-driven transcriptional programs
8 NRF2 antioxidant response ↑ NRF2 (adaptive, context-dependent) ↑ NRF2 (protective) Adaptive Stress compensation NRF2 induction reflects redox buffering rather than primary cytotoxicity


HK2, Hexokinase 2: Click to Expand ⟱
Source:
Type: enzyme
HK2 (Hexokinase 2) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. HK2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells.
HK2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells.
HK2 is a key regulatory enzyme in the glycolytic pathway.
HK2 plays a role in the regulation of glucose metabolism in diabetes.
HK2 is involved in the regulation of cell proliferation, apoptosis, and autophagy.

HK2 Inhibitors:
-2DG
-Curcumin
-Resveratrol
-EGCG
-Berberine
-Methyl Jasmonate (MJ)
-Honokiol
Scientific Papers found: Click to Expand⟱
2458- EGCG,  QC,    Identification of plant-based hexokinase 2 inhibitors: combined molecular docking and dynamics simulation studies
- Analysis, Nor, NA
HK2↓,
2431- QC,    The Protective Effect of Quercetin against the Cytotoxicity Induced by Fumonisin B1 in Sertoli Cells
- in-vitro, Nor, TM4
*Apoptosis↓, *ROS↓, *antiOx↓, *MMP↑, *GPI↑, *HK2↑, *ALDOA↑, *PKM1↑, *LDHA↑, *PFKL↑,
2344- QC,    Quercetin: A natural solution with the potential to combat liver fibrosis
- Review, Nor, NA
*HK2↓, *PFKP↓, *PKM2↓, *hepatoP↑, *ALAT↓, *AST↓, *Glycolysis↓, *lactateProd↓, *GlucoseCon↓, *CXCL1↓, *Inflam↓,
2342- QC,    Quercetin Inhibits the Proliferation of Glycolysis-Addicted HCC Cells by Reducing Hexokinase 2 and Akt-mTOR Pathway
- in-vitro, HCC, Bel-7402 - in-vitro, HCC, SMMC-7721 cell - in-vivo, NA, NA
TumCP↓, HK2↓, Akt↓, mTOR↓, GlucoseCon↓, lactateProd↓, Glycolysis↓,
2340- QC,    Oral Squamous Cell Carcinoma Cells with Acquired Resistance to Erlotinib Are Sensitive to Anti-Cancer Effect of Quercetin via Pyruvate Kinase M2 (PKM2)
- in-vitro, OS, NA
TumCG↓, GlucoseCon↓, TumCI↓, GLUT1↓, PKM2↓, LDHA↓, Glycolysis↓, lactateProd↓, HK2↓, eff↑,
2300- QC,    Flavonoids Targeting HIF-1: Implications on Cancer Metabolism
- Review, Var, NA
AntiTum↑, Hif1a↓, *Hif1a↑, Glycolysis↓, HK2↓, PDK3↓, PFKP?,
70- QC,    Quercetin inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells
- in-vitro, Pca, LNCaP - in-vitro, Pca, LAPC-4
PSA↓, AR↓, NKX3.1↓, HK2↓,
3374- QC,    Therapeutic effects of quercetin in oral cancer therapy: a systematic review of preclinical evidence focused on oxidative damage, apoptosis and anti-metastasis
- Review, Oral, NA - Review, AD, NA
α-SMA↓, α-SMA↑, TumCP↓, tumCV↓, TumVol↓, TumCI↓, TumMeta↓, TumCMig↓, ROS↑, Apoptosis↑, BioAv↓, *neuroP↑, *antiOx↑, *Inflam↓, *Aβ↓, *cardioP↑, MMP↓, Cyt‑c↑, MMP2↓, MMP9↓, EMT↓, MMPs↓, Twist↓, Slug↓, Ca+2↑, AIF↑, Endon↑, P-gp↓, LDH↑, HK2↓, PKA↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, GRP78/BiP↑, Casp12↑, CHOP↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

GlucoseCon↓, 3,   Glycolysis↓, 4,   HK2↓, 6,   lactateProd↓, 3,   LDH↑, 1,   LDHA↓, 1,   PDK3↓, 1,   PFKP?, 1,   PKM2↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Casp12↑, 1,   Cyt‑c↑, 1,   Endon↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   GRP78/BiP↑, 1,  

DNA Damage & Repair ⓘ

NKX3.1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 1,   mTOR↓, 1,   TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 1,   PKA↓, 1,   Slug↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   Twist↓, 1,   α-SMA↓, 1,   α-SMA↑, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

PSA↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   eff↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   LDH↑, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   TumVol↓, 1,  
Total Targets: 49

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 1,   ROS↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   ALDOA↑, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   GPI↑, 1,   HK2↓, 1,   HK2↑, 1,   lactateProd↓, 1,   LDHA↑, 1,   PFKL↑, 1,   PFKP↓, 1,   PKM1↑, 1,   PKM2↓, 1,  

Cell Death ⓘ

Apoptosis↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↑, 1,  

Immune & Inflammatory Signaling ⓘ

CXCL1↓, 1,   Inflam↓, 2,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,  
Total Targets: 27

Scientific Paper Hit Count for: HK2, Hexokinase 2
8 Quercetin
1 EGCG (Epigallocatechin Gallate)
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#:140  Target#:773  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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