condition found tbRes List
ART/DHA, Artemisinin: Click to Expand ⟱
Features:
Artemisinin a compound in a Chinese herb that may inhibit tumor growth and metastasis Artemisinin (antimalarial drugs)
Artesunic acid (Artesunate) , Dihydroartemisinin (DHA), artesunate, arteether, and artemether, SM735, SM905, SM933, SM934, and SM1044

The induction of OS in tumor cells via the production of ROS is the key mechanism of ART against cancer.
combination of ART and Nrf2 inhibitors to promote ferroptosis may have more efficient anticancer effects without damaging normal cells.

Summary:
- Pro-oxidant, mechanism related with iron (hence avoid supplements containing iron? Or perhaps take with iron?)
-ROS seems to affect both cancer and normal cells
- Delivery of artemisinin in conjugate form with transferrin or holotransferrin (serum iron transport proteins) have been shown to greatly improve its effectiveness.
- Potential direct inhibitor of STAT3
- Artemisinin synergized with the glycolysis inhibitor 2DG (2-deoxy- D -glucose)
ART Combined Therapy: Allicin, Resveratrol, Curcumin, VitC (but not orally at same time), Butyrate , 2-DG, Aminolevulinic AcidG
-possible problems with liver toxicity??

-Artesunate (ART), an artemisinin compound, is known for lysosomal degradation of ferritin, inducing oxidative stress and promoting cancer cell death.

Pathways:
- Increasing reactive oxygen species (ROS) production. This oxidative stress can cause the loss of mitochondrial membrane potential, leading to cytochrome c release and subsequent activation of caspase cascades.
- Downregulate HIF-1α
- By impairing glycolysis, artemisinin might force cells to rely on oxidative phosphorylation (OXPHOS) for energy production.
- Inhibit GLUT1 (glucose uptake), HK2, PKM2 (slow the glycolytic flux, thereby reducing the energy supply)

-Artemisinin has a half-life of about 3-4 hours, Artesunate 40 minutes and Artemether 12 hours. Peak plasma levels occur in 1-2 hour.
BioAv 21%, poor-good solubility. Artesunate (ART), a water soluble derivative of artemisinin. concentrations higher in blood, colon, liver, kidney (highly perfused organs)
Pathways:
- induce ROS production, iron dependent (affect both cancer and normal cells)
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Both Lowers (and raises) AntiOxidant defense in Cancer Cells: NRF2↓(contary), SOD↓, GSH↓ Catalase↓ GPx↓
- Small evidence of Raising AntiOxidant defense in Normal Cells: ROS↓(contary), NRF2↑, SOD↑(contary), GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, uPA↓, VEGF↓, ROCK1↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TOP1↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, ECAR↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- some small indication of inhibiting Cancer Stem Cells : CSC↓, Hh↓, β-catenin↓, sox2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK,
- Synergies: chemo-sensitization, RadioSensitizer, Others(review target notes),

- Selectivity: Cancer Cells vs Normal Cells


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⟱
2324- ART/DHA,    Research Progress of Warburg Effect in Hepatocellular Carcinoma
- Review, Var, NA
PKM2↓, DHA effectively suppressed aerobic glycolysis and ESCC progression by downregulating PKM2 expression in esophageal squamous cell carcinoma (ESCC) and ESCC cells
GLUT1↓, DHA inhibited leukemia cell K562 proliferation by suppressing GLUT1 and PKM2 levels, thereby regulating glucose uptake and inhibiting aerobic glycolysis
Glycolysis↓,
Akt↓, In LNCaP cells, DHA reduced Akt/mTOR and HIF-1α activity, leading to decreased expression of GLUT1, HK2, PKM2, and LDH and subsequent inhibition of aerobic glycolysis
mTOR↓,
Hif1a↓,
HK2↓,
LDH↓,
NF-kB↓, DHA was also found to inhibit the NF-κB signaling pathway to prevent GLUT1 translocation to the plasma membrane, thereby inhibiting the progression of non-small-cell lung cancer (NSCLC) cells via targeting glucose metabolism


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   GLUT1↓,1,   Glycolysis↓,1,   Hif1a↓,1,   HK2↓,1,   LDH↓,1,   mTOR↓,1,   NF-kB↓,1,   PKM2↓,1,  
Total Targets: 9

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: HK2, Hexokinase 2
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:34  Target#:773  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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