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


PARP, poly ADP-ribose polymerase (PARP) cleavage: Click to Expand ⟱
Source:
Type:
Poly (ADP-ribose) polymerase (PARP) cleavage is a hallmark of caspase activation. PARP (Poly (ADP-ribose) polymerase) is a family of proteins involved in a variety of cellular processes, including DNA repair, genomic stability, and programmed cell death. PARP enzymes play a crucial role in repairing single-strand breaks in DNA.
PARP has gained significant attention, particularly in the treatment of certain types of tumors, such as those with BRCA1 or BRCA2 mutations. These mutations impair the cell's ability to repair double-strand breaks in DNA through homologous recombination. Cancer cells with these mutations can become reliant on PARP for survival, making them particularly sensitive to PARP inhibitors.
PARP inhibitors, such as olaparib, rucaparib, and niraparib, have been developed as targeted therapies for cancers associated with BRCA mutations.

PARP Family:
The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes involved in a number of cellular processes, including DNA repair, genomic stability, and programmed cell death.
PARP1 is the predominant family member responsible for detecting DNA strand breaks and initiating repair processes, especially through base excision repair (BER).

PARP1 Overexpression:
In several cancer types—including breast, ovarian, prostate, and lung cancers—elevated PARP1 expression and/or activity has been reported.
High PARP1 expression in certain cancers has been associated with aggressive tumor behavior and resistance to therapies (especially those that induce DNA damage).
Increased PARP1 activity may correlate with poorer overall survival in tumors that rely on DNA repair for survival.
Scientific Papers found: Click to Expand⟱
2355- SK,    Pharmacological properties and derivatives of shikonin-A review in recent years
- Review, Var, NA
AntiCan↑, anticancer effects on various types of cancer by inhibiting cell proliferation and migration, inducing apoptosis, autophagy, and necroptosis.
TumCP↓,
TumCMig↓,
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
ROS↑, Shikonin also triggers Reactive Oxygen Species (ROS) generation
TrxR1↓, inhibiting the activation of TrxR1, PKM2, RIP1/3, Src, and FAK
PKM2↓,
RIP1↓,
RIP3↓,
Src↓,
FAK↓,
PI3K↓, modulating the PI3K/AKT/mTOR and MAPKs signaling;
Akt↓, shikonin induced a dose-dependent reduction of miR-19a to inhibit the activity of PI3K/AKT/mTOR pathway
mTOR↓,
GRP58↓, shikonin induced apoptosis in human myeloid cell line HL-60 cells through downregulating the expression of ERS protein ERP57 (42).
MMPs↓, hikonin suppressed cell migration through inhibiting the NF-κB pathway and reducing the expression of MMP-2 and MMP-9
ATF2↓, shikonin inhibited cell proliferation and tumor growth through suppressing the ATF2 pathway
cl‑PARP↑, shikonin significantly upregulated the expression of apoptosis-related proteins cleaved PARP and caspase-3 and increased cell apoptosis through increasing the phosphorylation of p38 MAPK and JNK, and inhibiting the phosphorylation of ERK
Casp3↑,
p‑p38↑,
p‑JNK↑,
p‑ERK↓,

2232- SK,    Shikonin Induces Autophagy and Apoptosis in Esophageal Cancer EC9706 Cells by Regulating the AMPK/mTOR/ULK Axis
- in-vitro, ESCC, EC9706
tumCV↓, Shikonin exposure repressed cell viability and migration and invasion capabilities and caused EC9706 cell autophagy and apoptosis by activating the AMPK/mTOR/ULK axis.
TumCMig↓,
TumCI↓,
TumAuto↑,
Apoptosis↑,
Bcl-2↓, Bcl-2 protein expressions were decreased; nevertheless, the protein expression of Bax, cleaved caspase3, cleaved caspase-8, and cleaved PARP were elevated with increasing concentrations of shikonin
BAX↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑PARP↑,
AMPK↑, Shikonin-Induced Autophagy and Apoptosis Through Activation of AMPK/mTOR/ULK Pathway
mTOR↑,
TumVol↓, The tumor diameter is reduced by more than 25%, the response rate is 37%, and the 1-year survival rate is 47%
OS↑,
LC3I↑, Similarly, shikonin can upregulate the protein expression of LC3 in EC9706 cells

2228- SK,    Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells
- in-vitro, CRC, HCT116 - in-vitro, CRC, HCT15 - in-vivo, NA, NA
Apoptosis↑, shikonin induced cell apoptosis by down-regulating BCL-2 and activating caspase-3/9 and the cleavage of PARP.
Bcl-2↓,
Casp3↑,
Casp9↑,
cl‑PARP↑,
GRP78/BiP↑, The expression of BiP and the PERK/elF2α/ATF4/CHOP and IRE1α /JNK signaling pathways were upregulated after shikonin treatment.
PERK↑,
eIF2α↑,
ATF4↑,
CHOP↑,
JNK↑,
eff↓, pre-treatment with N-acetyl cysteine significantly reduced the cytotoxicity of shikonin
ER Stress↑, Shikonin induced endoplasmic reticulum stress
ROS↑, Shikonin induced reactive oxygen species-mediated ER stress
TumCG↓, Shikonin suppressed the growth of colorectal cancer cells in vivo

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.

2469- SK,    Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2
- in-vitro, Lung, H1975
Apoptosis↑, Shikonin induced cell apoptosis and pyroptosis by triggering the activation of the caspase cascade and cleavage of poly (ADP-ribose) polymerase and gasdermin E by elevating intracellular ROS levels
Pyro↑,
Casp↑,
cl‑PARP↑,
GSDME↑,
ROS↑,
COX2↓, shikonin induced the degradation of COX-2 via the proteasome pathway, thereby decreasing COX-2 protein level and enzymatic activity and subsequently inhibiting the downstream PDK1/Akt and Erk1/2 signaling pathways through the induction of ROS produc
PDK1↓,
Akt↓,
ERK↓,
eff↓, Notably, COX-2 overexpression attenuated shikonin-induced apoptosis and pyroptosis
eff↓, NAC pre-treatment inhibited the shikonin-induced activation of the caspase cascade (caspase-8/9/3) and cleavage of PARP and GSDME in H1975 cells
eff↑, Celecoxib augmented the cytotoxic effects of shikonin by promoting the apoptosis and pyroptosis of H1975 cells

2010- SK,    Shikonin inhibits gefitinib-resistant non-small cell lung cancer by inhibiting TrxR and activating the EGFR proteasomal degradation pathway
- in-vitro, Lung, H1975 - in-vitro, Lung, H1650 - in-vitro, Nor, CCD19
EGFR↓, Shikonin is a potent inhibitor of EGFR
selectivity↑, Shikonin exhibited selective cytotoxicity among two NSCLC cell lines (H1975 and H1650) and one normal lung fibroblast cell line (CCD-19LU).
Casp↑, Shikonin significantly increased the activity of caspases and poly (ADP-ribosyl) polymerase (PARP), which are indicators of apoptosis
PARP↑,
Apoptosis↑,
ROS↑, intensity of ROS by greater than 10-fold
eff↓, NAC, an inhibitor of ROS, completely blocked apoptosis, caspase and PARP activation induced by Shikonin.
selectivity↑, the IC50 value of Shikonin in CCD19 (normal cells) is approximately 4-fold higher than that of HCC827, H1650 and H1975.

1344- SK,    Novel multiple apoptotic mechanism of shikonin in human glioma cells
- in-vitro, GBM, U87MG - in-vitro, GBM, Hs683 - in-vitro, GBM, M059K
ROS↑,
GSH↓,
MMP↓,
P53↑, upregulation of p53,
cl‑PARP↑,
Catalase↓,
SOD1↑,
Bcl-2↓,
BAX↑,
eff↓, Pretreatment with NAC, PFT-α, or cyclosporin A causes the recovery of shikonin-induced apoptosis.

1312- SK,    Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells
- in-vitro, OS, 143B
ROS↑, Taken together, our results reveal that shikonin increased ROS generation and ERK activation, and reduced Bcl2, which consequently caused the cells to undergo apoptosis.
p‑ERK↑, phosphorylated ERK was apparently increased in response to shikonin treatment for 24 and 48 h.
Bcl-2↓,
cl‑PARP↑, PARP cleavage, another well known characteristic of apoptosis, was also found in shikonin-treated cells.
Apoptosis↑,
TumCCA↑, 4 and 8mM shikonin for 24 h obviously caused G2/M phase arrest
Bcl-2↑, shikonin also decreased Bcl-2 expression, and decreased the pro-caspase 3
proCasp3↓,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Results for Effect on Cancer/Diseased Cells:
ADAM17↓,1,   Akt↓,2,   AMPK↑,1,   AntiCan↑,1,   Apoptosis↑,7,   ATF2↓,1,   ATF4↑,1,   BAX↑,2,   Bcl-2↓,4,   Bcl-2↑,1,   Casp↑,2,   Casp3↑,3,   cl‑Casp3↑,1,   proCasp3↓,1,   cl‑Casp8↑,1,   Casp9↑,1,   Catalase↓,1,   CHOP↑,1,   COX2↓,1,   cycD1↓,1,   cycE↓,1,   eff↓,6,   eff↑,1,   EGFR↓,1,   eIF2α↑,1,   p‑eIF2α↑,1,   ER Stress↑,1,   ERK↓,1,   p‑ERK↓,1,   p‑ERK↑,1,   FAK↓,1,   GRP58↓,1,   GRP78/BiP↑,1,   GSDME↑,1,   GSH↓,1,   IL6↓,1,   JAK1?,1,   p‑JAK1↓,1,   p‑JAK2↓,1,   JNK↑,1,   p‑JNK↑,1,   LC3I↑,1,   MMP↓,1,   MMPs↓,1,   mTOR↓,1,   mTOR↑,1,   Necroptosis↑,1,   OS↑,1,   p‑p38↑,1,   P53↑,1,   PARP↑,1,   cl‑PARP↑,7,   PDK1↓,1,   PERK↑,1,   PI3K↓,1,   PKM2↓,1,   Pyro↑,1,   RIP1↓,1,   RIP3↓,1,   ROS↑,7,   selectivity↑,2,   SOD1↑,1,   Src↓,1,   p‑STAT3↓,1,   TrxR1↓,1,   TumAuto↑,2,   TumCCA↑,2,   TumCG↓,2,   TumCI↓,1,   TumCMig↓,2,   TumCP↓,1,   tumCV↓,1,   TumVol↓,1,  
Total Targets: 73

Results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: PARP, poly ADP-ribose polymerase (PARP) cleavage
8 Shikonin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:239  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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