condition found tbRes List
SIL, Silymarin (Milk Thistle) silibinin: Click to Expand ⟱
Features:
Silymarin (Milk Thistle) Flowering herb related to daisy and ragweed family.
Silibinin (INN), also known as silybin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds.
-a flavonoid combination of 65–80% of seven flavolignans; the most important of these include silybin, isosilybin, silychristin, isosilychristin, and silydianin. Silybin is the most abundant compound in around 50–70% in isoforms silybin A and silybin B

-Note half-life 6hrs?.
BioAv not soluble in water, low bioA (1%). 240mg yielded only 0.34ug/ml plasma level. oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL, so can on acheive levels used in most in-vitro studies.
Pathways:
- results for both inducing and reducing ROS in cancer cells. In normal cell seems to consistently lower ROS. Given low bioavailability seems unlikely one could acheieve levels in vivo to raise ROS(except level in GUT could be much higher (800uM).
- ROS↑ related: MMP↓(ΔΨm), Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑,
- 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, uPA↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, β-catenin↓, Notch2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, 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


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⟱
1140- SIL,    Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth
- in-vitro, PC, AsPC-1 - in-vivo, PC, NA - in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3
TumCG↓,
Glycolysis↓,
cMyc↓,
STAT3↓,
TumCP↓,
Weight∅, prevents the loss of body weight and muscle.
Strength↑,
DNAdam↑,
Casp3↑,
Casp9↑,
GLUT1↓,
HK2↓,
LDHA↓,
GlucoseCon↓, silibinin inhibits glucose uptake and lactate release
lactateProd↓,
PPP↓, significant reduction in pentose phosphate pathway (PPP) metabolites, including 6-phosphogluconate (~50%), erythrose-4-phosphate (~40%), sedoheptulose-7-phosphate and sedoheptulose bis-phosphate (~ 70%)
Ki-67↓, reduced Ki67-positive cells
p‑STAT3↓,
cachexia↓,

2410- SIL,    Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vivo, NA, NA
TumAuto↑, Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis.
ATP↓,
Glycolysis↓, Silibinin suppressed glycolysis in glioma cells
H2O2↑, Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT
P53↑,
GSH↓,
xCT↓,
BNIP3↝, The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria
MMP↑, silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide
mt-ROS↑,
mtDam↑, Autophagy contributed to silibinin-induced mitochondria damage
HK2↓, protein levels of HK II, PFKP, and PKM2 were all downregulated time-dependently by silibinin in U87, U251, SHG-44, and C6 glioma cells
PFKP↓,
PKM2↓, silibinin suppressed glycolysis via downregulation of HK II, PFKP, and PKM2.
TumCG↓, Silibinin inhibited glioma cell growth in vivo


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

Results for Effect on Cancer/Diseased Cells:
ATP↓,1,   BNIP3↝,1,   cachexia↓,1,   Casp3↑,1,   Casp9↑,1,   cMyc↓,1,   DNAdam↑,1,   GlucoseCon↓,1,   GLUT1↓,1,   Glycolysis↓,2,   GSH↓,1,   H2O2↑,1,   HK2↓,2,   Ki-67↓,1,   lactateProd↓,1,   LDHA↓,1,   MMP↑,1,   mtDam↑,1,   P53↑,1,   PFKP↓,1,   PKM2↓,1,   PPP↓,1,   mt-ROS↑,1,   STAT3↓,1,   p‑STAT3↓,1,   Strength↑,1,   TumAuto↑,1,   TumCG↓,2,   TumCP↓,1,   Weight∅,1,   xCT↓,1,  
Total Targets: 31

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#:154  Target#:773  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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