condition found tbRes List
SK, Shikonin: Click to Expand ⟱
Features:
The (R)-enantiomer of alkannin is known as shikonin, and the racemic mixture of the two is known as shikalkin.
Shikonin is a naphthoquinone derivative primarily isolated from the roots of plants in the Boraginaceae family (e.g., Lithospermum erythrorhizon).
Shikonin is the main active component of a Chinese medicinal plant 'Zi Cao'
-Shikonin is a major component of zicao (purple gromwell, the dried root of Lithospermum erythrorhizon), a Chinese herbal medicine with anti-inflammatory properties
-Quinone methides (QMs) are highly reactive intermediates formed from natural compounds like shikonin
-ic50 cancer cells 1-10uM, normal cells >10uM

-known as Glycolysis inhibitor: ( inhibit pyruvate kinase M2 (PKM2*******), a key enzyme in the glycolytic pathway)

Available from mcsformulas.com Shikonin Pro Liposomal, 30 mg
Also In Glycolysis Inhibithree(100 mg PHLORIZIN,10 mg TANSHINONE IIA, 8 mg Shikonin)

-Note half-life15-30mins or 8hr?.
BioAv low, poor water solubility
Pathways:
- usually induce ROS production in cancer cells, and reduce ROS in normal cells.
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓,
- Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ GPx4↓
- 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↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK, P53↑,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells


CDK4, Cyclin-dependent kinase 4: Click to Expand ⟱
Source:
Type:
Cyclin-dependent kinase 4 (CDK4) is a key regulator of the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression and activity are often altered in various cancers, contributing to tumorigenesis.
CDK4 is frequently overexpressed in various cancers, and its expression levels can serve as a prognostic marker.
Scientific Papers found: Click to Expand⟱
3044- SK,    Shikonin Inhibits Non-Small-Cell Lung Cancer H1299 Cell Growth through Survivin Signaling Pathway
- in-vitro, Lung, H1299 - in-vitro, Lung, H460
TumCP↓, Results showed that shikonin inhibited the NSCLC H1299 cell proliferation in a dose-dependent manner.
survivin↓, Shikonin also inhibited the mRNA expression and protein level of survivin in H1299 cells
TumCCA↓, Shikonin arrested H1299 cell cycle at the G0/G1 phase by regulating CDK/cyclin family members
CDK2↓,
CDK4↓,
XIAP↓, shikonin regulated the expression of X-linked inhibitor of apoptosis- (XIAP-) mediated caspases 3 and 9, thus leading to the damage of mitochondrial membrane potential and induction of H1299 cell apoptosis.
Casp3↑, subsequently regulates the protein expression of XIAP/caspase 3/9, CDK2/4, and cyclin E/D1.
Casp9↑,
cycD1↓, downregulated the protein levels of CDK2, CDK4, cyclin E, and cyclin D1
cycE↓,

2191- SK,    Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation
- in-vitro, Melanoma, NA
PKM2↓, shikonin alone suppressed PKM2 activity
ATF4↓, Shikonin decreased the nuclear levels of ATF2 and knockdown of ATF2 suppressed the expression levels of Cdk4 and Fra-1
CDK4↓,
COX2↓, shikonin has been shown to inhibit TPA-induced cyclooxygenase-2 (COX-2) activation, which is mediated by suppression of MAPK signaling
MAPK↓,


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

Results for Effect on Cancer/Diseased Cells:
ATF4↓,1,   Casp3↑,1,   Casp9↑,1,   CDK2↓,1,   CDK4↓,2,   COX2↓,1,   cycD1↓,1,   cycE↓,1,   MAPK↓,1,   PKM2↓,1,   survivin↓,1,   TumCCA↓,1,   TumCP↓,1,   XIAP↓,1,  
Total Targets: 14

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: CDK4, Cyclin-dependent kinase 4
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:894  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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