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


TIMP2, Tissue Inhibitor of Metalloproteinases-2: Click to Expand ⟱
Source:
Type:
TIMP-2 has been shown to have distinct effects on cancer progression compared to TIMP-1. Research has suggested that TIMP-2 may have anti-tumor effects in certain types of cancer, including:
• Inhibiting tumor growth: TIMP-2 has been shown to inhibit the growth of tumor cells in vitro and in vivo.
High levels of TIMP-2 have been associated with better prognosis and improved survival in some cancers.
High levels of TIMP-2 have been associated with better prognosis and improved survival in some cancers.
High TIMP-2 expression: Breast, Lung, colorectal, Prostrate.
Low TIMP-2 expression: Ovarian, Pancreatic, Gastric.
Scientific Papers found: Click to Expand⟱
3391- ART/DHA,    Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug
- Review, Var, NA
TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB↓,
NF-kB↓,
cycD1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE↓,
E2Fs↓,
P21↑,
p27↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

556- ART/DHA,    Artemisinins as a novel anti-cancer therapy: Targeting a global cancer pandemic through drug repurposing
- Review, NA, NA
IL6↓,
IL1↓, IL-1β
TNF-α↓,
TGF-β↓, TGF-β1
NF-kB↓,
MIP2↓,
PGE2↓,
NO↓,
Hif1a↓,
KDR/FLK-1↓,
VEGF↓,
MMP2↓,
TIMP2↑,
ITGB1↑,
NCAM↑,
p‑ATM↑,
p‑ATR↑,
p‑CHK1↑,
p‑Chk2↑,
Wnt/(β-catenin)↓,
PI3K↓,
Akt↓,
ERK↓, ERK1/2
cMyc↓,
mTOR↓,
survivin↓,
cMET↓,
EGFR↓,
cycD1↓,
cycE1↓,
CDK4/6↓,
p16↑,
p27↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
oncosis↑,
TumCCA↑, G0/G1 into M phase, G0/G1 into S phase, G1 and G2/M
ROS↑, ovarian cancer cell line model, artesunate induced oxidative stress, DNA double-strand breaks (DSBs) and downregulation of RAD51 foci
DNAdam↑,
RAD51↓,
HR↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Results for Effect on Cancer/Diseased Cells:
ADP:ATP↑,1,   Akt↓,1,   angioG↓,1,   AP-1↓,1,   Apoptosis↑,1,   p‑ATM↑,1,   p‑ATR↑,1,   BAX↑,1,   BioAv↓,1,   BioAv↑,1,   Casp3↓,1,   Casp8↑,1,   Casp9↑,1,   CDC25↓,1,   Cdc42↑,1,   CDK2↓,1,   CDK4↓,1,   CDK4/6↓,1,   p‑CHK1↑,1,   p‑Chk2↑,1,   cMET↓,1,   cMyc↓,2,   COX2↓,1,   CycB↓,1,   cycD1↓,2,   cycE↓,1,   cycE1↓,1,   DNAdam↑,2,   E-cadherin↑,1,   E2Fs↓,1,   eff↓,1,   eff↑,1,   EGFR↓,1,   ER Stress↓,1,   ERK↓,2,   Ferroptosis↑,1,   GRP78/BiP↑,1,   Half-Life↓,1,   Hif1a↓,1,   HR↓,1,   IL1↓,1,   IL6↓,1,   IL8↓,1,   ITGB1↑,1,   JNK↓,1,   KDR/FLK-1↓,1,   MDM2↓,1,   MIP2↓,1,   MMP2↓,2,   MMP7↓,1,   MMP9↓,1,   mTOR↓,1,   NCAM↑,1,   NF-kB↓,2,   NO↓,1,   oncosis↑,1,   p16↑,1,   P21↑,1,   p27↑,2,   PCNA↓,1,   PGE2↓,1,   PI3K↓,1,   PKCδ↓,1,   RAD51↓,1,   Raf↓,1,   ROS↑,2,   selectivity↑,1,   survivin↓,2,   TGF-β↓,1,   TIMP2↑,2,   TNF-α↓,1,   TOP2↓,1,   TumAuto↑,1,   TumCCA↑,2,   TumCP↓,1,   TumMeta↓,1,   TumVol↓,1,   uPA↓,1,   VEGF↓,2,   Wnt/(β-catenin)↓,1,  
Total Targets: 80

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: TIMP2, Tissue Inhibitor of Metalloproteinases-2
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:34  Target#:308  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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