Database Query Results : Shikonin, , GlucoseCon

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)


GlucoseCon, Glucose Consumption: Click to Expand ⟱
Source:
Type:
Glucose consumption is often elevated in cancer cells due to an increased reliance on glycolysis for energy production, even in the presence of oxygen. This phenomenon, known as the Warburg effect, is a metabolic shift that allows cancer cells to rapidly proliferate and survive in nutrient-poor environments.

The increased glucose consumption in cancer cells can be detected using positron emission tomography (PET) scans, which measure the uptake of a glucose analog labeled with a radioactive tracer.
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↓, Shikonin treatment effectively suppressed cell proliferation and induced obvious cell apoptosis compared with the control.
Apoptosis↑,
TumCMig↓, Shikonin treatment suppressed cell migration and invasion effectively.
TumCI↓,
GlucoseCon↓, Shikonin treatment suppressed cell glucose uptake, lactate release and ATP level.
lactateProd↓,
ATP↓,
PKM2↓, activity of PKM2 was also largely inhibited by Shikonin
PI3K↓, PI3K/AKT signal pathway was inactivated by Shikonin treatment
Akt↓,
MMP3↓, MMP-3 and MMP-9 was decreased and the expression of TIMP was increased by Shikonin in HONE1 and SUNE-1 cells
MMP9↓,
TIMP1↑,

2357- SK,    GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism
- Study, HCC, NA - in-vivo, NA, NA
AntiTum↑, Shikonin exerted a remarkable antitumor effect in many tumors.
GTPBP4↓, We found that, first Shikonin could inhibit the binding of GTPBP4 and PKM2 proteins
PKM2↓,
lactateProd↓, increased lactate production and glucose consumption activity by GTPBP4 overexpression in PLC/PRF/5 and SMMC-7721 cells cells could be fully antagonized by Shikonin
GlucoseCon↓,
Glycolysis↓, Shikonin could suppress HCC growth and glycolysis through inhibiting PKM2 dependent glucose metabolism
E-cadherin↑, Downregulation of E-cadherin in GTPBP4 overexpression PLC/PRF/51 xenografts was also rescued by Shikonin treatment
TumCG↓, We found that Shikonin administration efficiently suppresses tumor growth in orthotopic xenograft mouse models of HCC

3045- SK,    Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2)
- in-vitro, PC, MIA PaCa-2
ECAR↓, Shikonin caused a concentration- and time-dependent inhibition of ECAR, which was more effective in highly glycolytic cells cultured in high-glucose (25 mM, Fig. 3ci) vs glucose-restricted cells (5 mM, Fig. 3cii).
Glycolysis↓, Collectively, these data suggest that shikonin exerts its cytotoxicity by inhibiting glycolysis and inducing ATP depletion, most likely due to inhibition of PKM2.
ATP↓, Only the highest concentration of shikonin (5 µM) induced a significant ATP depletion between 15 min and 6 h
PKM2↓,
TumCMig↓, Shikonin reduces PDAC cell migration
Ca+2↑, Shikonin induces cytotoxic Ca2+ overload
GlucoseCon↓, shikonin inhibited glucose consumption and lactate production with an IC50 of 5–10 μM in MCF-7 cells that exclusively express PKM2
lactateProd↓,
MMP↓, Shikonin is also reported to impair mitochondrial function and increase oxidative stress
ROS↑,

2419- SK,    Regulation of glycolysis and the Warburg effect in wound healing
- in-vivo, Nor, NA
Glycolysis↓, Treatment with 5–10 μM of the glycolysis inhibitor shikonin significantly decreased gene expression of the facilitative glucose transporters, GLUT1 and GLUT3
GLUT1↓,
GLUT3↓,
HK2↓, shikonin downregulated expression of the rate-limiting enzymes HK1 and HK2, although a 20 μM dose was needed
HK1↓, HK1
PFK1↓, Shikonin treatment also downregulated the rate-limiting enzyme PFK1
PFK2↓, PFK2 expression was only significantly lowered with a 20 μM dose
PKM2↓, 5 μM shikonin treatment inhibits gene expression of PKM2 (8.59 vs. 2.30, P < 0.001) and downregulated PDK1
lactateProd↓, coupled with decreased lactate production at higher concentrations of shikonin (10 μM and 20 μM)
GlucoseCon↓, shikonin effectively downregulated key enzymes involved in glucose uptake, glycolysis, and lactate production

2418- SK,    Experimental Study of Hepatocellular Carcinoma Treatment by Shikonin Through Regulating PKM2
- in-vitro, HCC, SMMC-7721 cell - in-vitro, HCC, HUH7 - in-vitro, HCC, HepG2
tumCV↓, The results of CCK-8 showed that shikonin significantly inhibited cell viability of HCC cells.
GlucoseCon↓, The levels of glucose uptake and lactate production were dramatically decreased by shikonin-treated.
lactateProd↓,
ChemoSen↑, shikonin enhanced the anti-cancer effect of sorafenib in vitro and in vivo.
PKM2↓, By inhibiting PKM2, shikonin inhibited proliferation and glycolysis and induced cell apoptosis in HCC cells.
Glycolysis↓,

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↓, Shikonin treatment decreased the proliferation, migration, invasion, glucose uptake, lactate levels, ATP levels and PFKFB2 expression levels and increased apoptosis in lung cancer cells in a dose‑dependent manner.
TumCMig↓,
TumCI↓,
GlucoseCon↓,
lactateProd↓,
PFKFB2↓,
Warburg↓, shikonin inhibited the Warburg effect and exerted antitumor activity in lung cancer cells, which was associated with the downregulation of PFKFB2 expression.
GLUT1∅, while the expression levels of the other proteins (PDK1, GLUT1, PGK2, LDHA, PKM2, GLUT3, PDH and p-PDH) were not altered by shikonin treatment.
LDHA∅,
PKM2∅,
GLUT3∅,
PDH∅,

2185- SK,    Shikonin Inhibits Tumor Growth in Mice by Suppressing Pyruvate Kinase M2-mediated Aerobic Glycolysis
- in-vitro, Lung, LLC1 - in-vitro, Melanoma, B16-BL6 - in-vivo, NA, NA
Glycolysis↓, confirming the inhibitory effect of shikonin on tumor aerobic glycolysis
GlucoseCon↓, shikonin dose-dependently inhibited glucose uptake and lactate production in Lewis lung carcinoma (LLC) and B16 melanoma cells
lactateProd↓,
PKM2↓, suppression of cell aerobic glycolysis by shikonin is through decreasing PKM2 activity
selectivity↑, shikonin treatment significantly promoted tumor cell apoptosis compared to untreated control cells.
Warburg↓, agreement with previous findings of shikonin as a Warburg effect inhibitor
TumVol↓, A significant reduction of tumor size (Fig. 7B) and weight (Fig. 7C) was observed when shikonin was injected at concentration of 1 or 10 mg/kg.
TumW↓,

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↓, shikonin inhibited the viability, proliferation, invasion, and migration of NSCLC cells A549 and PC9, and induced apoptosis.
TumCP↓,
TumCI↓,
TumCMig↓,
Apoptosis↑,
PKM2↓, As the inhibitor of pyruvate kinase M2 (PKM2), a key enzyme in glycolysis, shikonin inhibited glucose uptake and the production of lactate
Glycolysis↓,
GlucoseCon↓,
lactateProd↓,
ChemoSen↑, In vivo chemotherapeutic assay showed that shikonin reduced the tumor volume and weight in NSCLC mice model and increased the sensitivity to cisplatin chemotherapy.
TumVol↓,
TumW↓,
GLUT1↓, combination of shikonin and cisplatin downregulated the expression of PKM2 and its transcriptionally regulated downstream gene glucose transporter 1 (Glut1) in tumor tissue

2181- SK,    Shikonin and its analogs inhibit cancer cell glycolysis by targeting tumor pyruvate kinase-M2
- in-vitro, BC, MCF-7 - in-vitro, Lung, A549 - in-vitro, Cerv, HeLa
Glycolysis↓, Shikonin and alkannin significantly inhibited the glycolytic rate, as manifested by cellular lactate production and glucose consumption in drug-sensitive and resistant cancer cell lines
lactateProd↓,
GlucoseCon↓,
PKM2↓, shikonin and alkannin are the most potent and specific inhibitors to PKM2 reported so far
LDH∅, LDH was not inhibited by shikonin, alkannin and the analogs

2200- SK,    Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis
- in-vitro, Thyroid, CAL-62 - in-vitro, Thyroid, 8505C
NF-kB↓, SKN inhibits the expression of NF-κB,GPX4,TXNRD1,PKM2,GLUT1.
GPx4↓,
TrxR1↓, TXNRD1
PKM2↓,
GLUT1↓,
Glycolysis↓, inhibiting glycolysis in ATC cells.
Ferroptosis↑, SKN in inducing intracellular ferroptosis
GlucoseCon↓, Measurements of glucose uptake after 1, 3, and 5 μM concentrations of SKN treatment for 24 h showed a decrease in both cells
lactateProd↓, Lactate production in the cells decreased with the rise of SKN treatment concentration
ROS↑, cellular ROS increased significantly with the rise in SKN concentration

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↓, Shikonin effectively inhibited cell proliferation in dose-dependent and time-dependent manner compared with the control group
Glycolysis↓, detection of glycolysis showed that Shikonin suppressed the glucose consumption, lactate production, glycolytic intermediates and pyruvate kinase enzymatic activity.
GlucoseCon↓,
lactateProd↓,
PKM2↓,
p‑PKM2↓, decreased the expression of p-PKM2 and p-STAT3 in vivo
p‑STAT3↓,
GLUT1↓, Shikonin suppressed the expression of GLUT1 and HK2 proteins which are related to glycolysis.
HK2↓,
TumW↓, tumor weight in the Shikonin group decreased by approximately 40% compared with the vehicle control group,


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 1,   HK1↓, 1,   ROS↑, 2,   TrxR1↓, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 2,   MMP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ECAR↓, 1,   GlucoseCon↓, 11,   Glycolysis↓, 9,   HK2↓, 2,   lactateProd↓, 11,   LDH∅, 1,   LDHA∅, 1,   PDH∅, 1,   PFK1↓, 1,   PFK2↓, 1,   PFKFB2↓, 1,   PKM2↓, 10,   PKM2∅, 1,   p‑PKM2↓, 1,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 2,   Ferroptosis↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 2,  

Proliferation, Differentiation & Cell State ⓘ

GTPBP4↓, 1,   PI3K↓, 1,   p‑STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP3↓, 1,   MMP9↓, 1,   TIMP1↑, 1,   TumCI↓, 3,   TumCMig↓, 4,   TumCP↓, 4,  

Barriers & Transport ⓘ

GLUT1↓, 4,   GLUT1∅, 1,   GLUT3↓, 1,   GLUT3∅, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

LDH∅, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,   TumVol↓, 2,   TumW↓, 3,  
Total Targets: 49

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: GlucoseCon, Glucose Consumption
11 Shikonin
1 Cisplatin
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#:623  State#:%  Dir#:%
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