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


MMP2, metalloproteinase-2: Click to Expand ⟱
Source:
Type:
Matrix metalloproteinase-2 (MMP-2) is an enzyme that plays a significant role in the degradation of extracellular matrix components, which is crucial for various physiological processes, including tissue remodeling, wound healing, and angiogenesis.
Elevated levels of MMP-2 have been associated with poor prognosis in various cancers, including breast, lung, and colorectal cancers.
MMP2 and MMP9: two enzymes are critical to tumor invasion.
Scientific Papers found: Click to Expand⟱
3041- SK,    Promising Nanomedicines of Shikonin for Cancer Therapy
- Review, Var, NA
Glycolysis↓, SHK could regulate immunosuppressive tumor microenvironment through inhibiting glycolysis of tumor cells and repolarizing tumor-associated macrophages (TAMs).
TAMS↝,
BioAv↓, HK is a hydrophobic natural molecule with unsatisfactory solubility, rapid intestinal absorption, obvious “first pass” effect, and rapid clearance, leading to low oral bioavailability.
Half-Life↝, SHK displays a half-life of 15.15 ± 1.41 h and Cmax of 0.94 ± 0.11 μg/ml in rats when administered intravenously.
P21↑, Table 1
ERK↓,
ROS↑,
GSH↓,
MMP↓,
TrxR↓,
MMP13↓,
MMP2↓,
MMP9↓,
SIRT2↑,
Hif1a↓,
PKM2↓,
TumCP↓, Inhibit Cell Proliferation
TumMeta↓, Inhibit Cells Metastasis and Invasion
TumCI↓,

2210- SK,    Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway
- in-vitro, BC, MGC803
TumCA↓, Shikonin (1 μm) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells.
TumCI↓,
TumCMig↓,
MMP2↓, matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-κB
MMP7↓,
TLR2↓,
p65↓,
NF-kB↓,
eff↑, In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone.
ROS↑, Shikonin-induced ROS generation


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

Results for Effect on Cancer/Diseased Cells:
BioAv↓,1,   eff↑,1,   ERK↓,1,   Glycolysis↓,1,   GSH↓,1,   Half-Life↝,1,   Hif1a↓,1,   MMP↓,1,   MMP13↓,1,   MMP2↓,2,   MMP7↓,1,   MMP9↓,1,   NF-kB↓,1,   P21↑,1,   p65↓,1,   PKM2↓,1,   ROS↑,2,   SIRT2↑,1,   TAMS↝,1,   TLR2↓,1,   TrxR↓,1,   TumCA↓,1,   TumCI↓,2,   TumCMig↓,1,   TumCP↓,1,   TumMeta↓,1,  
Total Targets: 26

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: MMP2, metalloproteinase-2
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:201  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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