Shikonin / TumCP Cancer Research Results

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
Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance
1 PKM2-mediated aerobic glycolysis (Warburg metabolism) ↓ Energy / biomass restriction Key, repeatedly reported mechanism: shikonin suppresses PKM2 activity and PKM2-driven glycolysis in multiple tumor models, with downstream growth inhibition and apoptosis
2 ROS accumulation / oxidative stress ↑ ROS Redox overload Common upstream trigger that drives mitochondrial dysfunction and regulated cell death programs; often precedes necroptosis/apoptosis signaling
3 Necroptosis core cascade (RIPK1 → RIPK3 → MLKL) ↑ Programmed necrotic cell death Strong evidence across cancers (e.g., leukemia and nasopharyngeal carcinoma): shikonin increases RIPK1/RIPK3/MLKL expression/activation; necroptosis inhibitors can blunt the effect
4 Mitochondrial integrity (ΔΨm) ↓ Mitochondrial dysfunction ROS-linked depolarization; acts as a pivot into intrinsic apoptosis and other death programs
5 Intrinsic apoptosis (BAX/BAK → Caspase-9/3) ↑ Programmed cell death Frequently observed; often framed as ROS → mitochondrial damage → caspase-dependent apoptosis
6 PKM2/STAT3 signaling axis ↓ Reduced survival & proliferation signaling In ESCC and related models, shikonin suppresses PKM2-driven glycolysis and down-modulates STAT3 pathway activity
7 NF-κB pathway ↓ Reduced pro-survival transcription Reported as part of multi-target suppression of inflammatory/anti-apoptotic programs in several tumor models and reviews
8 PI3K–AKT (± mTOR) ↓ Growth & resistance pathway inhibition Often described as sensitizing cells to apoptosis/TRAIL; may be secondary to oxidative stress and metabolic collapse
9 Stress MAPKs (JNK / p38) ↑ Pro-death stress signaling Common downstream response to ROS; can reinforce apoptosis and other death outcomes
10 Ferroptosis-related axis (lipid peroxidation; GPX4) ↑ lipid perox / ↓ GPX4 Iron-dependent oxidative death Reported prominently for acetylshikonin (a shikonin derivative): ROS-associated lipid peroxidation with reduced GPX4 expression alongside RIPK1/RIPK3/MLKL activation
11 Endoplasmic reticulum stress (UPR / ERS) ↑ Proteotoxic stress signaling Frequently mentioned in leukemia-focused mechanism summaries and broader reviews as contributory to growth arrest and death
12 Multiple regulated death programs (apoptosis / necroptosis / ferroptosis / pyroptosis) ↑ (context-dependent) Broader cell-death engagement Recent reviews emphasize that shikonin can engage several programmed cell death modalities depending on cell context and dosing
Rank Pathway / Target Axis Direction Primary Effect Notes / Cancer Relevance Ref
1 PKM2-mediated aerobic glycolysis (Warburg metabolism) ↓ PKM2 activity / ↓ glycolysis Energy & biomass restriction Demonstrates shikonin (and analogs) inhibit cancer glycolysis, reducing glucose consumption/lactate production via PKM2 targeting (ref)
2 PKM2 → STAT3 signaling axis ↓ PKM2-driven signaling / ↓ STAT3 pathway Reduced survival & proliferation ESCC study: shikonin suppresses PKM2-mediated aerobic glycolysis and regulates PKM2/STAT3 signaling (ref)
3 Necroptosis (RIPK1 → RIPK3 → MLKL) ↑ RIPK1/RIPK3/MLKL Programmed necrotic cell death Nasopharyngeal carcinoma: shikonin induces necroptosis with upregulation of RIPK1/RIPK3/MLKL (with ROS involvement) (ref)
4 ROS accumulation ↑ ROS Oxidative stress trigger Colon cancer model: shikonin increases intracellular ROS; ROS functions upstream of apoptosis (ref)
5 Mitochondrial apoptosis (Caspase-9/3) ↑ Caspase-9/3 Programmed cell death Same colon cancer study shows shikonin increases caspase-3 and caspase-9 activity (mitochondria-mediated apoptosis) (ref)
6 ER stress / UPR (PERK → eIF2α → CHOP) ↑ Proteotoxic stress apoptosis signaling Colon cancer: shikonin-induced apoptosis mediated by PERK/eIF2α/CHOP ER-stress pathway (ref)
7 Autophagic flux (autophagosome–lysosome completion) ↓ autophagic flux (blocked) ROS + apoptosis amplification Colorectal cancer: shikonin induces ROS and apoptosis by inhibiting autophagic flux (ref)
8 NF-κB signaling ↓ NF-κB activity Reduced pro-survival transcription Pancreatic cancer xenograft/mechanistic study: shikonin suppresses NF-κB activity and NF-κB–regulated gene products (ref)
9 PI3K–AKT–mTOR (stemness / chemoresistance axis) ↓ PI3K/AKT/mTOR Reduced survival & stemness Chemoresistant lung cancer CSC context: shikonin attenuates PI3K–Akt–mTOR pathway and reduces cancer stemness (ref)
10 Cell cycle control (p21; G2/M arrest) ↑ p21 / ↑ G2/M arrest Proliferation block Gastric cancer (AGS): shikonin induces cell-cycle arrest linked to p21 regulation (ref)
11 Invasion / metastasis programs (NF-κB-linked) ↓ invasion Anti-invasive phenotype Reports shikonin inhibits tumor invasion via down-regulation of NF-κB–related mechanisms in a high-metastatic tumor model (ref)
12 Chemosensitization via glycolysis suppression ↓ glycolysis / ↑ cisplatin sensitivity Combination benefit NSCLC: shikonin inhibits glycolysis and sensitizes cells to cisplatin (explicitly connecting metabolic suppression to chemosensitization) (ref)


TumCP, Tumor Cell proliferation: Click to Expand ⟱
Source:
Type:
Tumor cell proliferation is a key characteristic of cancer. It refers to the rapid and uncontrolled growth of cells that can lead to the formation of tumors.
Scientific Papers found: Click to Expand⟱
2360- SK,    Shikonin inhibits growth, invasion and glycolysis of nasopharyngeal carcinoma cells through inactivating the phosphatidylinositol 3 kinase/AKT signal pathway
- in-vitro, NPC, HONE1 - in-vitro, NPC, SUNE-1
TumCP↓, Apoptosis↑, TumCMig↓, TumCI↓, GlucoseCon↓, lactateProd↓, ATP↓, PKM2↓, PI3K↓, Akt↓, MMP3↓, MMP9↓, TIMP1↑,
2355- SK,    Pharmacological properties and derivatives of shikonin-A review in recent years
- Review, Var, NA
AntiCan↑, TumCP↓, TumCMig↓, Apoptosis↑, TumAuto↑, Necroptosis↑, ROS↑, TrxR1↓, PKM2↓, RIP1↓, RIP3↓, Src↓, FAK↓, PI3K↓, Akt↓, mTOR↓, GRP58↓, MMPs↓, ATF2↓, cl‑PARP↑, Casp3↑, p‑p38↑, p‑JNK↑, p‑ERK↓,
2234- SK,    Shikonin Suppresses Cell Tumorigenesis in Gastric Cancer Associated with the Inhibition of c-Myc and Yap-1
- in-vitro, GC, NA
TumCP↓, TumCI↓, TumCMig↓, cMyc↓, YAP/TEAD↓,
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↑, TumAuto↑, TumCP↓, TumCCA↑, P21↑, cycD1/CCND1↓, ER Stress↑, p‑eIF2α↑, CHOP↑, cl‑Casp3↑, p38↑, LC3B-II↑, Beclin-1↑, ROS↑, eff↓,
2227- SK,    Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species
- in-vitro, GC, BGC-823 - in-vitro, GC, SGC-7901 - in-vitro, Nor, GES-1
selectivity↑, TumCP↓, TumCD↑, ROS↑, MMP↓, Casp↑, Cyt‑c↑, Endon↑, AIF↑, eff↓, ChemoSen↑, TumCCA↑, GSH/GSSG↓, lipid-P↑,
2221- SK,    Shikonin Induces Apoptosis, Necrosis, and Premature Senescence of Human A549 Lung Cancer Cells through Upregulation of p53 Expression
- in-vitro, Lung, A549
Apoptosis↑, TumCP↓, tumCV↓, Necroptosis↑, P53↑, ROS↑, NF-kB↓,
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↓, survivin↓, TumCCA↓, CDK2↓, CDK4↓, XIAP↓, Casp3↑, Casp9↑, cycD1/CCND1↓, cycE/CCNE↓,
5104- SK,    Shikonin induces cell cycle arrest in human gastric cancer (AGS) by early growth response 1 (Egr1)-mediated p21 gene expression.
- in-vitro, GC, AGS
TumCP↓, TumCCA↑, P21↑,
5103- SK,    Attenuation of PI3K-Akt-mTOR Pathway to Reduce Cancer Stemness on Chemoresistant Lung Cancer Cells by Shikonin and Synergy with BEZ235 Inhibitor
- in-vitro, NSCLC, A549
CSCs↓, TumCP↓, Nanog↓, OCT4↓, p‑Akt↓, P70S6K↓, PI3K↓, mTOR↓, eff↑,
5101- SK,    Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis
- vitro+vivo, CRC, SW-620 - vitro+vivo, CRC, HCT116
Apoptosis↑, TumAuto↑, Gal1↑, TumCP↓, ROS↑, eff↑,
5100- SK,    Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expression
- vitro+vivo, NPC, NA
TumCP↓, RIP1↑, ROS↑, Necroptosis↑, Casp3↑, Casp8↑, eff↓, TumCG↓,
3051- SK,    Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation
- Review, Var, NA
Nrf1↑, Apoptosis↑, TumCP↓, eff⇅, chemoP↑, eff↑, VCAM-1↓, Hif1a↓,
3046- SK,    Shikonin attenuates lung cancer cell adhesion to extracellular matrix and metastasis by inhibiting integrin β1 expression and the ERK1/2 signaling pathway
- in-vitro, Lung, A549
TumCP↓, TumCI↓, TumCMig↓, p‑ERK↓, ITGB1↓,
3041- SK,    Promising Nanomedicines of Shikonin for Cancer Therapy
- Review, Var, NA
Glycolysis↓, TAMS↝, BioAv↓, Half-Life↝, P21↑, ERK↓, ROS↑, GSH↓, MMP↓, TrxR↓, MMP13↓, MMP2↓, MMP9↓, SIRT2↑, Hif1a↓, PKM2↓, TumCP↓, TumMeta↓, TumCI↓,
2417- SK,    Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer
- in-vitro, Lung, A549 - in-vitro, Lung, H446
TumCP↓, TumCMig↓, TumCI↓, GlucoseCon↓, lactateProd↓, PFKFB2↓, Warburg↓, GLUT1∅, LDHA∅, PKM2∅, GLUT3∅, PDH∅,
2182- SK,  Cisplatin,    Shikonin inhibited glycolysis and sensitized cisplatin treatment in non-small cell lung cancer cells via the exosomal pyruvate kinase M2 pathway
- in-vitro, Lung, A549 - in-vitro, Lung, PC9 - in-vivo, NA, NA
tumCV↓, TumCP↓, TumCI↓, TumCMig↓, Apoptosis↑, PKM2↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, ChemoSen↑, TumVol↓, TumW↓, GLUT1↓,
1073- SK,  Chemo,    Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells
- in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3
PAK1↓, TumCP↓, Apoptosis↑, ChemoSen↑, ROS↑,
2203- SK,    Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation
- in-vitro, Lung, NA
TumCP↓, Apoptosis↓, TumCMig↓, TumCI↓, Ferroptosis↑, ERK↓, GPx4↓, 4-HNE↑, ROS↑, GSH↓, ATF3↑, HDAC1↓, ac‑Histones↑,
965- SK,    Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signaling
- in-vitro, CRC, HCT116 - in-vitro, CRC, SW-620
Hif1a↓, ROS↓, mTOR↓, p70S6↓, 4E-BP1↓, eIF2α↓, TumCCA↑, TumCP↓, Half-Life↝,
2198- SK,    Shikonin suppresses proliferation of osteosarcoma cells by inducing ferroptosis through promoting Nrf2 ubiquitination and inhibiting the xCT/GPX4 regulatory axis
- in-vitro, OS, MG63 - in-vitro, OS, 143B
TumCP↓, TumCCA↑, Ferroptosis↑, Iron↑, ROS↑, lipid-P↑, MDA↑, mtDam↑, NRF2↓, xCT↓, GPx4↓, GSH/GSSG↓, Keap1↑,
2195- SK,    Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axis
- in-vitro, OS, NA
TumCP↓, Ferroptosis↓, Hif1a↑, HO-1↑, Iron↑, ROS↑, GSH/GSSG↓, GPx4↓,
2192- SK,    Shikonin Inhibits Tumor Growth of ESCC by suppressing PKM2 mediated Aerobic Glycolysis and STAT3 Phosphorylation
- in-vitro, ESCC, KYSE-510 - in-vitro, ESCC, Eca109 - in-vivo, NA, NA
TumCP↓, Glycolysis↓, GlucoseCon↓, lactateProd↓, PKM2↓, p‑PKM2↓, p‑STAT3↓, GLUT1↓, HK2↓, TumW↓,
2190- SK,    Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1α signaling pathway
- in-vitro, HCC, HCCLM3
TumCP↓, TumCMig↓, TumCI↓, Apoptosis↑, MMP↓, ROS↑, OCR↓, ATP↓, PKM2↓,

Showing Research Papers: 1 to 23 of 23

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 23

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

4-HNE↑, 1,   ATF3↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 2,   GPx4↓, 3,   GSH↓, 2,   GSH/GSSG↓, 3,   HO-1↑, 1,   Iron↑, 2,   Keap1↑, 1,   lipid-P↑, 2,   MDA↑, 1,   Nrf1↑, 1,   NRF2↓, 1,   ROS↓, 1,   ROS↑, 12,   TrxR↓, 1,   TrxR1↓, 1,   xCT↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP↓, 2,   MMP↓, 3,   mtDam↑, 1,   OCR↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   GlucoseCon↓, 4,   Glycolysis↓, 3,   ac‑Histones↑, 1,   HK2↓, 1,   lactateProd↓, 4,   LDHA∅, 1,   PDH∅, 1,   PFKFB2↓, 1,   PKM2↓, 6,   PKM2∅, 1,   p‑PKM2↓, 1,   SIRT2↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 9,   ATF2↓, 1,   Casp↑, 1,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   Endon↑, 1,   Ferroptosis↓, 1,   Ferroptosis↑, 2,   GRP58↓, 1,   p‑JNK↑, 1,   Necroptosis↑, 3,   p38↑, 1,   p‑p38↑, 1,   RIP1↓, 1,   RIP1↑, 1,   survivin↓, 1,   TumCD↑, 1,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

p70S6↓, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   eIF2α↓, 1,   p‑eIF2α↑, 1,   ER Stress↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3B-II↑, 1,   TumAuto↑, 3,  

DNA Damage & Repair ⓘ

P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 3,   TumCCA↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

4E-BP1↓, 1,   CSCs↓, 1,   ERK↓, 2,   p‑ERK↓, 2,   HDAC1↓, 1,   mTOR↓, 3,   Nanog↓, 1,   OCT4↓, 1,   P70S6K↓, 1,   PI3K↓, 3,   Src↓, 1,   p‑STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

FAK↓, 1,   ITGB1↓, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP3↓, 1,   MMP9↓, 2,   MMPs↓, 1,   PAK1↓, 1,   RIP3↓, 1,   TIMP1↑, 1,   TumCI↓, 8,   TumCMig↓, 8,   TumCP↓, 23,   TumMeta↓, 1,   VCAM-1↓, 1,  

Angiogenesis & Vasculature ⓘ

Hif1a↓, 3,   Hif1a↑, 1,   TAMS↝, 1,  

Barriers & Transport ⓘ

GLUT1↓, 2,   GLUT1∅, 1,   GLUT3∅, 1,  

Immune & Inflammatory Signaling ⓘ

Gal1↑, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 3,   eff↓, 3,   eff↑, 3,   eff⇅, 1,   Half-Life↝, 2,   selectivity↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoP↑, 1,   TumVol↓, 1,   TumW↓, 2,  
Total Targets: 128

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: TumCP, Tumor Cell proliferation
23 Shikonin
1 Cisplatin
1 Chemotherapy
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:150  Target#:327  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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