Shikonin / PKM2 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)


PKM2, Pyruvate Kinase, Muscle 2: Click to Expand ⟱
Source:
Type: enzyme
PKM2 (Pyruvate Kinase, Muscle 2) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. PKM2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells.
-C-myc is a common oncogene that enhances aerobic glycolysis in the cancer cells by transcriptionally activating GLUT1, HK2, PKM2 and LDH-A
-PKM2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells.
-inhibition of PKM2 may cause ATP depletion and inhibiting glycolysis.
-PK exists in four isoforms: PKM1, PKM2, PKR, and PKL
-PKM2 plays a role in the regulation of glucose metabolism in diabetes.
-PKM2 is involved in the regulation of cell proliferation, apoptosis, and autophagy.
– Pyruvate kinase catalyzes the final, rate-limiting step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate with the production of ATP.
– The PKM2 isoform is uniquely regulated and can exist in both highly active tetrameric and less active dimeric forms.
– Cancer cells often favor the dimeric form of PKM2 to slow pyruvate production, thereby accumulating upstream glycolytic intermediates that can be diverted into anabolic pathways to support cell growth and proliferation.
– Under low oxygen conditions, cancer cells rely on altered metabolic pathways in which PKM2 is a key player. – The shift to aerobic glycolysis (Warburg effect) orchestrated in part by PKM2 helps tumor cells survive and grow in hypoxic conditions.

– Elevated expression of PKM2 is frequently observed in many cancer types, including lung, breast, colorectal, and pancreatic cancers.
– High levels of PKM2 are often correlated with enhanced tumor aggressiveness, poor differentiation, and advanced clinical stage.

PKM2 in carcinogenesis and oncotherapy

Inhibitors of PKM2:
-Shikonin, Resveratrol, Baicalein, EGCG, Apigenin, Curcumin, Ursolic Acid, Citrate (best known as an allosteric inhibitor of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme in glycolysis) potential to directly inhibit or modulate PKM2 is less well established

Full List of PKM2 inhibitors from Database
-key connected observations: Glycolysis↓, lactateProd↓, ROS↑ in cancer cell, while some result for opposite effect on normal cells.
Tumor pyruvate kinase M2 modulators

Flavonoids effect on PKM2
Compounds name IC50/AC50uM Effect
Flavonols
1. Fisetin 0.90uM Inhibition
2. Rutin 7.80uM Inhibition
3. Galangin 8.27uM Inhibition
4. Quercetin 9.24uM Inhibition
5. Kaempferol 9.88uM Inhibition
6. Morin hydrate 37.20uM Inhibition
7. Myricetin 0.51uM Activation
8. Quercetin 3-b- D-glucoside 1.34uM Activation
9. Quercetin 3-D -galactoside 27-107uM Ineffective
Flavanons
10. Neoeriocitrin 0.65uM Inhibition
11. Neohesperidin 14.20uM Inhibition
12. Naringin 16.60uM Inhibition
13. Hesperidin 17.30uM Inhibition
14. Hesperitin 29.10uM Inhibition
15. Naringenin 70.80uM Activation
Flavanonols
16. (-)-Catechin gallateuM 0.85 Inhibition
17. (±)-Taxifolin 1.16uM Inhibition
18. (-)-Epicatechin 1.33uM Inhibition
19. (+)-Gallocatechin 4-16uM Ineffective
Phenolic acids
20. Ferulic 11.4uM Inhibition
21. Syringic and 13.8uM Inhibition
22. Caffeic acid 36.3uM Inhibition
23. 3,4-Dihydroxybenzoic acid 78.7uM Inhibition
24. Gallic acid 332.6uM Inhibition
25. Shikimic acid 990uM Inhibition
26. p-Coumaric acid 22.2uM Activation
27. Sinapinic acids 26.2uM Activation
28. Vanillic 607.9uM Activation


Scientific Papers found: Click to Expand⟱
2364- SK,    Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation
- in-vivo, PSA, NA
eff↑, lactateProd↓, PKM2↓,
2363- SK,    Inhibition of PKM2 by shikonin impedes TGF-β1 expression by repressing histone lactylation to alleviate renal fibrosis
- in-vivo, CKD, NA
PKM2↓, lactateProd↓, TGF-β↓,
2362- SK,    RIP1 and RIP3 contribute to shikonin-induced glycolysis suppression in glioma cells via increase of intracellular hydrogen peroxide
- in-vitro, GBM, U87MG - in-vivo, GBM, NA - in-vitro, GBM, U251
RIP1↑, RIP3↑, Glycolysis↓, G6PD↓, HK2↓, PKM2↓, H2O2↑, GSH↓, ROS↑,
2361- SK,    Natural shikonin and acetyl-shikonin improve intestinal microbial and protein composition to alleviate colitis-associated colorectal cancer
- in-vivo, CRC, NA
GutMicro↑, Dose↝, IL1β↓, IL6↓, TNF-α↓, PKM2↓,
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↑,
2359- SK,    Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery
- in-vivo, Liver, NA
TumCG↓, PKM2↓, EMT↓, TGF-β↓, Glycolysis↓, lactateProd↓, ATP↓,
2358- SK,    SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2
- in-vivo, Park, NA
*eff↑, *PKM2↓, *motorD↑, *lactateProd↓,
2357- SK,    GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism
- Study, HCC, NA - in-vivo, NA, NA
AntiTum↑, GTPBP4↓, PKM2↓, lactateProd↓, GlucoseCon↓, Glycolysis↓, E-cadherin↑, TumCG↓,
2356- SK,    ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment
- in-vitro, Ovarian, CaOV3 - in-vitro, Ovarian, OV90 - in-vivo, NA, NA
PKM2↓, Glycolysis↓, FASN↓, lactateProd↓, Warburg↓, TumCG↓, VM↓,
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↓,
2354- SK,    PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation
- in-vivo, Sepsis, NA
PKM2↓, *PKM2↓, *IL1β↓, *IL18↓, *HMGB1↓, *Casp1↓, *NLRP3↓, *AIM2↓, *p‑eIF2α↓, *Sepsis↓,
2370- SK,    The role of pyruvate kinase M2 in anticancer therapeutic treatments
- Review, Var, NA
Glycolysis↓, PKM2↓, EGFR↓, PI3K↓, p‑Akt↓, Hif1a↓,
2223- SK,    Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review
- in-vitro, Var, NA
PKM2↓,
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↓, Glycolysis↓, ATP↓, PKM2↓, TumCMig↓, Ca+2↑, GlucoseCon↓, lactateProd↓, MMP↓, ROS↑,
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↓,
3040- SK,    Pharmacological Properties of Shikonin – A Review of Literature since 2002
- Review, Var, NA - Review, IBD, NA - Review, Stroke, NA
*Half-Life↝, *BioAv↓, *BioAv↑, *BioAv↑, *Inflam↓, *TNF-α↓, *other↑, *MPO↓, *COX2↓, *NF-kB↑, *STAT3↑, *antiOx↑, *ROS↓, *neuroP↑, *SOD↑, *Catalase↑, *GPx↑, *Bcl-2↑, *BAX↓, cardioP↑, AntiCan↑, NF-kB↓, ROS↑, PKM2↓, TumCCA↑, Necroptosis↑, Apoptosis↑, DNAdam↑, MMP↓, Cyt‑c↑, LDH↝,
2470- SK,    PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism
- in-vitro, Lung, H1299
PKM2↓, PDK1↓, Glycolysis↓,
2420- SK,    Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury
- in-vivo, AKI, NA
PKM2↓, other↝,
2419- SK,    Regulation of glycolysis and the Warburg effect in wound healing
- in-vivo, Nor, NA
Glycolysis↓, GLUT1↓, GLUT3↓, HK2↓, HK1↓, PFK1↓, PFK2↓, PKM2↓, lactateProd↓, GlucoseCon↓,
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↓, GlucoseCon↓, lactateProd↓, ChemoSen↑, PKM2↓, Glycolysis↓,
2416- SK,    Shikonin induces cell death by inhibiting glycolysis in human testicular cancer I-10 and seminoma TCAM-2 cells
- in-vitro, Testi, TCAM-2
MMP↓, ROS↑, lactateProd↓, Bcl-2↓, cl‑Casp3↓, PKM2↓, GLUT1↓, HK2↓, LC3B↑,
2415- SK,    Shikonin induces programmed death of fibroblast synovial cells in rheumatoid arthritis by inhibiting energy pathways
- in-vivo, Arthritis, NA
Apoptosis?, TumAuto↑, ROS↑, ATP↓, Glycolysis↓, PI3K↓, Akt↓, mTOR↓, *Apoptosis↓, *Inflam↓, *TNF-α↓, *IL6↓, *IL8↓, *IL10↓, *IL17↓, *hepatoP↑, *RenoP↑, PKM2↓, GLUT1↓, HK2↓,
2187- SK,  VitK3,    Shikonin, vitamin K3 and vitamin K5 inhibit multiple glycolytic enzymes in MCF-7 cells
- in-vitro, BC, MCF-7
Glycolysis↓, PKM2↓,
2186- SK,    Shikonin differentially regulates glucose metabolism via PKM2 and HIF1α to overcome apoptosis in a refractory HCC cell line
- in-vitro, HCC, HepG2 - in-vitro, HCC, HCCLM3
Glycolysis↓, PKM2↓, Apoptosis↑, ROS↑, OXPHOS⇅, eff↓,
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↓, GlucoseCon↓, lactateProd↓, PKM2↓, selectivity↑, Warburg↓, TumVol↓, TumW↓,
2184- SK,  Cisplatin,    PKM2 Inhibitor Shikonin Overcomes the Cisplatin Resistance in Bladder Cancer by Inducing Necroptosis
- in-vitro, CRC, T24/HTB-9
PKM2↓, ChemoSen↑, Necroptosis↑,
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↓,
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↓, lactateProd↓, GlucoseCon↓, PKM2↓, LDH∅,
1050- SK,    Shikonin improves the effectiveness of PD-1 blockade in colorectal cancer by enhancing immunogenicity via Hsp70 upregulation
- in-vitro, Colon, CT26
HSP70/HSPA5↑, ROS↑, PKM2↓,
1049- SK,    Shikonin inhibits immune checkpoint PD-L1 expression on macrophage in sepsis by modulating PKM2
- in-vivo, NA, NA
TNF-α↓, IL6↓, IFN-γ↓, IL1β↓, PD-L1↓, p‑PKM2↓,
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↓, GPx4↓, TrxR1↓, PKM2↓, GLUT1↓, Glycolysis↓, Ferroptosis↑, GlucoseCon↓, lactateProd↓, ROS↑,
2197- SK,    Shikonin derivatives for cancer prevention and therapy
- Review, Var, NA
ROS↑, Ca+2↑, BAX↑, Bcl-2↓, MMP9↓, NF-kB↓, PKM2↓, Hif1a↓, NRF2↓, P53↑, DNMT1↓, MDR1↓, COX2↓, VEGF↓, EMT↓, MMP7↓, MMP13↓, uPA↓, RIP1↑, RIP3↑, Casp3↑, Casp7↑, Casp9↑, P21↓, DFF45↓, TRAIL↑, PTEN↑, mTOR↓, AR↓, FAK↓, Src↓, Myc↓, RadioS↑,
2196- SK,    Research progress in mechanism of anticancer action of shikonin targeting reactive oxygen species
- Review, Var, NA
*ALAT↓, *AST↓, *Inflam?, *EMT↑, ROS?, TrxR1↓, PERK↑, eIF2α↑, ATF4↑, CHOP↑, IRE1↑, JNK↑, eff↝, DR5↑, Glycolysis↓, PKM2↓, ChemoSen↑, GPx4↓, HO-1↑,
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↓, TumCCA↑, Apoptosis↑, EGFR↓, PI3K↓, Hif1a↓, PKM2↓, cycD1/CCND1↓, AntiTum↑,
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↓,
2191- SK,    Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation
- in-vitro, Melanoma, NA
PKM2↓, ATF4↓, CDK4↓, COX2↓, MAPK↓,
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↓,
2189- SK,    PKM2 inhibitor shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells
- in-vitro, Melanoma, NA
PKM2↓, chemoPv↑, eff↝, lactateProd↓, ROS↑, *ROS?, *PKM2↓,

Showing Research Papers: 1 to 38 of 38

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 38

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,   GPx4↓, 2,   GSH↓, 2,   H2O2↑, 1,   HK1↓, 1,   HO-1↑, 1,   NRF2↓, 1,   OXPHOS⇅, 1,   ROS?, 1,   ROS↑, 13,   TrxR↓, 1,   TrxR1↓, 3,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 5,   MMP↓, 5,   OCR↓, 1,  

Core Metabolism/Glycolysis ⓘ

ECAR↓, 1,   FASN↓, 1,   G6PD↓, 1,   GlucoseCon↓, 10,   Glycolysis↓, 19,   HK2↓, 5,   lactateProd↓, 16,   LDH↝, 1,   LDH∅, 1,   PDK1↓, 1,   PFK1↓, 1,   PFK2↓, 1,   PKM2↓, 36,   p‑PKM2↓, 2,   SIRT2↑, 1,   Warburg↓, 2,  

Cell Death ⓘ

Akt↓, 3,   p‑Akt↓, 1,   Apoptosis?, 1,   Apoptosis↑, 7,   ATF2↓, 1,   BAX↑, 1,   Bcl-2↓, 2,   Casp3↑, 2,   cl‑Casp3↓, 1,   Casp7↑, 1,   Casp9↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   Ferroptosis↑, 1,   GRP58↓, 1,   JNK↑, 1,   p‑JNK↑, 1,   MAPK↓, 1,   Myc↓, 1,   Necroptosis↑, 3,   p‑p38↑, 1,   RIP1↓, 1,   RIP1↑, 2,   TRAIL↑, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,   tumCV↓, 3,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   eIF2α↑, 1,   HSP70/HSPA5↑, 1,   IRE1↑, 1,   PERK↑, 1,  

Autophagy & Lysosomes ⓘ

LC3B↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DFF45↓, 1,   DNAdam↑, 1,   DNMT1↓, 1,   P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 1,   P21↓, 1,   P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

EMT↓, 2,   ERK↓, 1,   p‑ERK↓, 1,   GTPBP4↓, 1,   mTOR↓, 3,   PI3K↓, 5,   PTEN↑, 1,   Src↓, 2,   p‑STAT3↓, 1,   TumCG↓, 3,  

Migration ⓘ

Ca+2↑, 2,   E-cadherin↑, 1,   FAK↓, 2,   MMP13↓, 2,   MMP2↓, 1,   MMP3↓, 1,   MMP7↓, 1,   MMP9↓, 3,   MMPs↓, 1,   RIP3↓, 1,   RIP3↑, 2,   TGF-β↓, 2,   TIMP1↑, 1,   TumCI↓, 4,   TumCMig↓, 5,   TumCP↓, 6,   TumMeta↓, 1,   uPA↓, 1,  

Angiogenesis & Vasculature ⓘ

ATF4↓, 1,   ATF4↑, 1,   EGFR↓, 2,   Hif1a↓, 4,   TAMS↝, 1,   VEGF↓, 1,   VM↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 6,   GLUT3↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IFN-γ↓, 1,   IL1β↓, 2,   IL6↓, 2,   NF-kB↓, 3,   PD-L1↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 4,   Dose↝, 1,   eff↓, 1,   eff↑, 1,   eff↝, 2,   Half-Life↝, 1,   MDR1↓, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 2,   GutMicro↑, 1,   IL6↓, 2,   LDH↝, 1,   LDH∅, 1,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 2,   cardioP↑, 1,   chemoPv↑, 1,   TumVol↓, 2,   TumW↓, 3,  
Total Targets: 143

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   MPO↓, 1,   ROS?, 1,   ROS↓, 1,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   lactateProd↓, 1,   PKM2↓, 3,  

Cell Death ⓘ

Apoptosis↓, 1,   BAX↓, 1,   Bcl-2↑, 1,   Casp1↓, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,  

Protein Folding & ER Stress ⓘ

p‑eIF2α↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1,   STAT3↑, 1,  

Immune & Inflammatory Signaling ⓘ

AIM2↓, 1,   COX2↓, 1,   HMGB1↓, 1,   IL10↓, 1,   IL17↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam?, 1,   Inflam↓, 2,   NF-kB↑, 1,   TNF-α↓, 2,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 2,   eff↑, 1,   Half-Life↝, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AST↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

hepatoP↑, 1,   motorD↑, 1,   neuroP↑, 1,   RenoP↑, 1,  

Infection & Microbiome ⓘ

Sepsis↓, 1,  
Total Targets: 44

Scientific Paper Hit Count for: PKM2, Pyruvate Kinase, Muscle 2
38 Shikonin
2 Cisplatin
1 VitK3,menadione
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#:772  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

Home Page