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


cycD1, cyclin D1 pathway: Click to Expand ⟱
Source:
Type:
Also called CCND1
The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression.
Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.
Cyclin D1 is often found to be overexpressed in various cancers.
Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.
Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.
In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.
Scientific Papers found: Click to Expand⟱
2229- SK,    Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways
- in-vitro, Melanoma, A375
Apoptosis↑, Shikonin induces apoptosis and autophagy in A375 cells and inhibits their proliferation
TumAuto↑,
TumCP↓,
TumCCA↑, Shikonin caused G2/M phase arrest through upregulation of p21 and downregulation of cyclin B1
P21↑,
cycD1↓,
ER Stress↑, Shikonin significantly triggered ER stress-mediated apoptosis by upregulating the expression of p-eIF2α, CHOP, and cleaved caspase-3.
p‑eIF2α↑,
CHOP↑,
cl‑Casp3↑,
p38↑, induced protective autophagy by activating the p38 pathway, followed by an increase in the levels of p-p38, LC3B-II, and Beclin 1
LC3B-II↑,
Beclin-1↑,
ROS↑, Shikonin increased the production of reactive oxygen species
eff↓, NAC treatment significantly decreased the expression of p-p38, LC3B-II, and Beclin 1.

2230- SK,    Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer
- in-vitro, CRC, HCT116 - in-vivo, NA, NA
TumCG↓, shikonin suppressed the growth of colon cancer cells in a dose-dependent manner in vitro and in vivo
Bcl-2↓, Shikonin induced mitochondria-mediated apoptosis, which was regulated by Bcl-2 family proteins.
ROS↑, found that shikonin dose-dependently increased the generation of intracellular ROS in colon cancer cells
Bcl-xL↓, generation of ROS, down-regulated expression of Bcl-2 and Bcl-xL, depolarization of the mitochondrial membrane potential and activation of the caspase cascade
MMP↓,
Casp↑,
selectivity↑, shikonin presented minimal toxicity to non-neoplastic colon cells and no liver injury in xenograft models
cycD1↓, Cyclin D expression was decreased with shikonin treatment
TumCCA↑, induced cell growth inhibition by the induction G1 cell cycle arrest.
eff↓, NAC or GSH could block the shikonin-dependent burst of intracellular ROS

3047- SK,    Shikonin suppresses colon cancer cell growth and exerts synergistic effects by regulating ADAM17 and the IL-6/STAT3 signaling pathway
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW48
TumCG↓, SKN inhibited colon cancer cell growth, suppressed both constitutive and IL-6-induced STAT3 phosphorylation, and downregulated the expression of ADAM17
p‑STAT3↓,
ADAM17↓,
Apoptosis↑, SKN promoted cell apoptosis, as evidenced by increased expression levels of cleaved caspase-3 and cleaved PARP in both cell lines
Casp3↑,
cl‑PARP↑,
cycD1↓, SKN decreased the expression of cyclin D1 and cyclin E1, thus suggesting the disruption of the cell cycle and the suppression of cell growth
cycE↓,
TumCCA↑,
JAK1?, The inhibitory effects of SKN on the phosphorylation of both JAK1 and JAK2 in the two cell lines were also observed
p‑JAK1↓,
p‑JAK2↓,
p‑eIF2α↑, phosphorylation levels of eIF2α were enhanced by SKN (20 µM) in the HCT116 and SW480 colon cancer cells
eff↓, NAC decreased SKN-induced p-eIF2α expression and reversed the SKN-mediated downregulation of ADAM17 protein expression
ROS↑, suppressed the expression of ADAM17 mediated by ROS-associated p-eIF2α expression in the HCT116 and SW480 colon cancer cells
IL6↓, demonstrated that the antitumor effects of SKN on colon cancer cells were associated with its inhibition of the IL-6/STAT3 signaling pathway.

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↓,

2194- SK,    Efficacy of Shikonin against Esophageal Cancer Cells and its possible mechanisms in vitro and in vivo
- in-vitro, ESCC, Eca109 - in-vitro, ESCC, EC9706 - in-vivo, NA, NA
tumCV↓, Shikonin reduced esophageal cancer cells viability and induced cell cycle arrest and apoptosis.
TumCCA↑,
Apoptosis↑,
EGFR↓, Shikonin decreased EGFR, PI3K, p-AKT, HIF1α and PKM2 expression
PI3K↓,
Hif1a↓,
PKM2↓,
cycD1↓, shikonin reduced the expression of PKM2, HIF1α and cyclinD1 in tumor tissues
AntiTum↑, shikonin has a powerful antitumor effect in vivo.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Results for Effect on Cancer/Diseased Cells:
ADAM17↓,1,   AntiTum↑,1,   Apoptosis↑,3,   Bcl-2↓,1,   Bcl-xL↓,1,   Beclin-1↑,1,   Casp↑,1,   Casp3↑,2,   cl‑Casp3↑,1,   Casp9↑,1,   CDK2↓,1,   CDK4↓,1,   CHOP↑,1,   cycD1↓,5,   cycE↓,2,   eff↓,3,   EGFR↓,1,   p‑eIF2α↑,2,   ER Stress↑,1,   Hif1a↓,1,   IL6↓,1,   JAK1?,1,   p‑JAK1↓,1,   p‑JAK2↓,1,   LC3B-II↑,1,   MMP↓,1,   P21↑,1,   p38↑,1,   cl‑PARP↑,1,   PI3K↓,1,   PKM2↓,1,   ROS↑,3,   selectivity↑,1,   p‑STAT3↓,1,   survivin↓,1,   TumAuto↑,1,   TumCCA↓,1,   TumCCA↑,4,   TumCG↓,2,   TumCP↓,2,   tumCV↓,1,   XIAP↓,1,  
Total Targets: 42

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: cycD1, cyclin D1 pathway
5 Shikonin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:73  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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