Shikonin 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)

Scientific Papers found: Click to Expand⟱

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∅,

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,

 paw swelling in rat arthritic tissues

Apoptosis?, TumAuto↑, ROS↑, ATP↓, Glycolysis↓, PI3K↓, Akt↓, mTOR↓, *Apoptosis↓, *Inflam↓, *TNF-α↓, *IL6↓, *IL8↓, *IL10↓, *IL17↓, *hepatoP↑, *RenoP↑, PKM2↓, GLUT1↓, HK2↓,

1346-

SK,

An Oxidative Stress Mechanism of Shikonin in Human Glioma Cells

in-vitro,

GBM,

U87MG

2, 8, 50 and 100 μM

in-vitro,

GBM,

Hs683

NRF2↓, ROS↑, Apoptosis↑, Cyt‑c↑, GSH↓, MMP↓, P53↑, HO-1⇅,

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

10 μM

in-vitro,

Melanoma,

B16-BL6

in-vivo,

NA,

mouse

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↑,

2183-

SK,

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

in-vitro,

Thyroid,

TPC-1

0.744 μg/mL

TumCMig↓, TumCI↓, PTEN↑, DNMT1↓,

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

2 µM, 4 µM, 6 µM, and 8 µM

5.739 µM

in-vitro,

Lung,

PC9

6.302 µM

in-vivo,

NA,

mice

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

0-20uM for 1 h

0.3 mM,

in-vitro,

Lung,

A549

in-vitro,

Cerv,

HeLa

Glycolysis↓, lactateProd↓, GlucoseCon↓, PKM2↓, LDH∅,

2011-

SK,

Shikonin Attenuates Acetaminophen-Induced Hepatotoxicity by Upregulation of Nrf2 through Akt/GSK3β Signaling

in-vitro,

Nor,

HL7702

L-02

in-vivo,

Nor,

mice

*NRF2↑, *hepatoP↑, *ALAT↓, *AST↓, *MPO↓, *ROS↓, *GSH↑,

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

2.6uM

in-vitro,

Lung,

H1650

3.9uM

in-vitro,

Nor,

CCD19

12.2uM

Normal cells, shows selectivity

EGFR↓, selectivity↑, Casp↑, PARP↑, Apoptosis↑, ROS↑, eff↓, selectivity↑,

2009-

SK,

Necroptosis inhibits autophagy by regulating the formation of RIP3/p62/Keap1 complex in shikonin-induced ROS dependent cell death of human bladder cancer

in-vitro,

Bladder,

TumCG↓, selectivity↑, *toxicity∅, Necroptosis↑, ROS↑, p62↑, Keap1↑, *NRF2↑, eff↑,

2008-

SK,

Cisplatin,

Enhancement of cisplatin-induced colon cancer cells apoptosis by shikonin, a natural inducer of ROS in vitro and in vivo

in-vitro,

CRC,

HCT116

in-vivo,

NA,

mice

ChemoSen↑, selectivity↑, i-ROS↑, DNAdam↑, MMP↓, TumCCA↑, eff↓, *toxicity↓,

2007-

SK,

Shikonin Directly Targets Mitochondria and Causes Mitochondrial Dysfunction in Cancer Cells

in-vitro,

lymphoma,

U937

<10uM

in-vitro,

BC,

MCF-7

in-vitro,

BC,

SkBr3

in-vitro,

CRC,

HCT116

in-vitro,

OS,

U2OS

NA,

Nor,

RPE-1

RPE-1-GFP-EB3 cells were treated with 25 μM shikonin

tumCV↓, selectivity↑, Dose↝, other↑, MMP↓, ROS↑, DNAdam↑, Ca+2↑, Casp9↑, Cyt‑c↑, *toxicity↓,

2188-

SK,

Molecular mechanism of shikonin inhibiting tumor growth and potential application in cancer treatment

Review,

Var,

ROS↑, EGFR↓, PI3K↓, Akt↓, angioG↓, Apoptosis↑, Necroptosis↑, GSH↓, Ca+2↓, MMP↓, ERK↓, p38↑, proCasp3↑, eff↓, VEGF↓, FOXO3↑, EGR1↑, SIRT1↑, RIP1↑, RIP3↑, BioAv↓, NF-kB↓, Half-Life↓,

1345-

SK,

The Critical Role of Redox Homeostasis in Shikonin-Induced HL-60 Cell Differentiation via Unique Modulation of the Nrf2/ARE Pathway

in-vitro,

AML,

HL-60

100 ng/mL

CD14↑, CD11b↑, ROS↑, GSH↓, GSH/GSSG↓, GPx↑, Catalase↓, Diff↑,

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↑, cl‑PARP↑, Catalase↓, SOD1↑, Bcl-2↓, BAX↑, eff↓,

1343-

SK,

Simple ROS-responsive micelles loaded Shikonin for efficient ovarian cancer targeting therapy by disrupting intracellular redox homeostasis

in-vitro,

Ovarian,

A2780S

in-vivo,

NA,

A2780S

mice

*BioAv↓, ROS↑, GSH↓, TumCG↓,

1342-

SK,

RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen species

in-vitro,

GBM,

in-vivo,

NA,

mice

RIP1↑, RIP3↑, DNAdam↑, ROS↑, GSH↓,

1312-

SK,

Shikonin induces apoptosis through reactive oxygen species/extracellular signal-regulated kinase pathway in osteosarcoma cells

in-vitro,

OS,

143B

0-8uM

2.01microM

ROS↑, p‑ERK↑, Bcl-2↓, cl‑PARP↑, Apoptosis↑, TumCCA↑, Bcl-2↑, proCasp3↓,

1284-

SK,

Shikonin induces ferroptosis in multiple myeloma via GOT1-mediated ferritinophagy

in-vitro,

Melanoma,

RPMI-8226

in-vitro,

Melanoma,

U266

Ferroptosis↑, LDH↓, ROS↑, Iron↑, lipid-P↑, ATP↓, HMGB1↓, GPx4↓, MDA↑, SOD↓, GSH↓,

1281-

SK,

Enhancement of NK cells proliferation and function by Shikonin

in-vivo,

Colon,

Caco-2

mice

Perforin↑, GranB↑, p‑ERK↑, p‑Akt↑, NK cell↑, eff↝,

1280-

SK,

Shikonin Induces Apoptotic Cell Death via Regulation of p53 and Nrf2 in AGS Human Stomach Carcinoma Cells

in-vitro,

GC,

AGS

35–250 nM

ROS↑, Casp3↑, P53↑, NRF2↓,

1073-

SK,

Chemo,

Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells

in-vitro,

PC,

PANC1

7.252 ± 0.054 μM

in-vitro,

PC,

Bxpc-3

PAK1↓, TumCP↓, Apoptosis↑, ChemoSen↑, ROS↑,

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,

sepsis mice

TNF-α↓, IL6↓, IFN-γ↓, IL1β↓, PD-L1↓, p‑PKM2↓,

977-

SK,

A novel antiestrogen agent Shikonin inhibits estrogen-dependent gene transcription in human breast cancer cells

in-vitro,

BC,

T47D

SK (1-5uM) for 24 h

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF-7

in-vitro,

Nor,

HMEC

TumCG↓, ERα/ESR1↓, selectivity↑, *toxicity↓,

2201-

SK,

Shikonin promotes ferroptosis in HaCaT cells through Nrf2 and alleviates imiquimod-induced psoriasis in mice

in-vitro,

PSA,

HaCaT

in-vivo,

NA,

mice

*eff↑, *IL6↓, *IL17↓, *TNF-α↓, *lipid-P↑, *NRF2↓, *HO-1↝, *NCOA4↝, *GPx4↓, *Ferroptosis↓, *Inflam↓, *ROS↓, *Iron↓,

2218-

SK,

Shikonin Alleviates Endothelial Cell Injury Induced by ox-LDL via AMPK/Nrf2/HO-1 Signaling Pathway

in-vitro,

Nor,

HUVECs

*Dose↝, *Apoptosis↓, *Casp3↓, *Bcl-2↑, *Inflam↓, *VCAM-1↓, *ICAM-1↓, *E-sel↓, *ROS↓, *SOD↑, *AMPK↑, *NRF2↑, *HO-1↑, *TNF-α↓, *IL1β↓, *IL6↓,

2217-

SK,

Shikonin Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis to Attenuate Renal Ischemia/Reperfusion Injury by Activating the Sirt1/Nrf2/HO-1 Pathway

in-vivo,

Nor,

mice

in-vitro,

Nor,

HK-2

*ER Stress↓, *SIRT1↑, *NRF2↑, *HO-1↑, *eff↓, *RenoP↑, *GRP78/BiP↓, *CHOP↓, *Casp12↓, *BAX↓, *cl‑Casp3↓,

2216-

SK,

Shikonin upregulates the expression of drug-metabolizing enzymes and drug transporters in primary rat hepatocytes

in-vivo,

Nor,

 0-2 μM

Sprague-Dawley rats

*NRF2↑, *AhR↑, *CYP1A1↑, *CYP1A2↑, *CYP2C6↑, *CYP2D1↑, *CYP3A2↑, *NQO1↑,

2215-

SK,

doxoR,

Shikonin alleviates doxorubicin-induced cardiotoxicity via Mst1/Nrf2 pathway in mice

in-vivo,

Nor,

mice

*cardioP↑, *ROS↓, *Inflam↓, *Mst1↓, *NRF2↑, *eff↓, *antiOx↑, *SOD↑, *GSH↑, *TNF-α↓, BAX↓, Bcl-2↑,

2214-

SK,

Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway

in-vitro,

Nor,

0-10uM

*NRF2↑, *HO-1↑, *NQO1↑, *antiOx↑, *neuroP↑, *ROS↓, *MDA↓, *SOD↑, GSH↑,

2213-

SK,

Shikonin attenuates cerebral ischemia/reperfusion injury via inhibiting NOD2/RIP2/NF-κB-mediated microglia polarization and neuroinflammation

in-vivo,

Stroke,

 MCAO/R rats

*neuroP↑, *Inflam↓, *iNOS↓, *TNF-α↓, *IL1β↓, *IL6↓, *ARG↑, *TGF-β↑, *IL10↑, *NF-kB↓, *eff↓,

2212-

SK,

Shikonin Exerts an Antileukemia Effect against FLT3-ITD Mutated Acute Myeloid Leukemia Cells via Targeting FLT3 and Its Downstream Pathways

in-vitro,

AML,

FLT3↓, NF-kB↓, miR-155↓, Diff↑, TumCG↓,

2211-

SK,

Shikonin mitigates ovariectomy-induced bone loss and RANKL-induced osteoclastogenesis via TRAF6-mediated signaling pathways

in-vivo,

ostP,

mice, RANKL-induced

*BMD↑, *p‑NF-kB↓, *p‑p50↓, *p‑p65↓, *p‑ERK↓, *p‑cJun↓, *p‑p38↓,

2210-

SK,

Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway

in-vitro,

BC,

MGC803

1.854 μm

TumCA↓, TumCI↓, TumCMig↓, MMP2↓, MMP7↓, TLR2↓, p65↓, NF-kB↓, eff↑, ROS↑,

2209-

SK,

Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cells

in-vitro,

adrenal,

ACC-M

(0, 2.5, 5, 10 μM) for 24 h

MMP9↓, NF-kB↓, IKKα↓,

2203-

SK,

Shikonin suppresses small cell lung cancer growth via inducing ATF3-mediated ferroptosis to promote ROS accumulation

in-vitro,

Lung,

TumCP↓, Apoptosis↓, TumCMig↓, TumCI↓, Ferroptosis↑, ERK↓, GPx4↓, 4-HNE↑, ROS↑, GSH↓, ATF3↑, HDAC1↓, ac‑Histones↑,

2202-

SK,

Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification

in-vitro,

Var,

Iron↑, Ferroptosis↑, pH↝, H2O2↑, ROS↑, Fenton↑, GSH↓, GPx4↓, lipid-P↑,

965-

SK,

Shikonin suppresses proliferation and induces cell cycle arrest through the inhibition of hypoxia-inducible factor-1α signaling

in-vitro,

CRC,

HCT116

(0.3 to 30 uM)

shikonin did not adversely affect cell viability up to a concentration of 10 uM

in-vitro,

CRC,

SW-620

Hif1a↓, ROS↓, mTOR↓, p70S6↓, 4E-BP1↓, eIF2α↓, TumCCA↑, TumCP↓, Half-Life↝,

2200-

SK,

Shikonin inhibits the growth of anaplastic thyroid carcinoma cells by promoting ferroptosis and inhibiting glycolysis

in-vitro,

Thyroid,

CAL-62

1, 3 and 5 μM SKN for 24 h

in-vitro,

Thyroid,

8505C

NF-kB↓, GPx4↓, TrxR1↓, PKM2↓, GLUT1↓, Glycolysis↓, Ferroptosis↑, GlucoseCon↓, lactateProd↓, ROS↑,

2199-

SK,

Induction of Ferroptosis by Shikonin in Gastric Cancer via the DLEU1/mTOR/GPX4 Axis

in-vitro,

GC,

ROS↑, lipid-P↑, Iron↑, MDA↑, GPx4↓, Ferritin↓, DLEU1↓, mTOR↓, Ferroptosis↑,

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

 0.75 uM, 1.5 uM and 3 uM

1.432 uM

in-vitro,

OS,

143B

1.638 uM

TumCP↓, TumCCA↑, Ferroptosis↑, Iron↑, ROS↑, lipid-P↑, MDA↑, mtDam↑, NRF2↓, xCT↓, GPx4↓, GSH/GSSG↓, Keap1↑,

2197-

SK,

Shikonin derivatives for cancer prevention and therapy

Review,

Var,

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,

*ALAT↓, *AST↓, *Inflam?, *EMT↑, ROS?, TrxR1↓, PERK↑, eIF2α↑, ATF4↑, CHOP↑, IRE1↑, JNK↑, eff↝, DR5↑, Glycolysis↓, PKM2↓, ChemoSen↑, GPx4↓, HO-1↑,

2195-

SK,

Shikonin induces ferroptosis in osteosarcomas through the mitochondrial ROS-regulated HIF-1α/HO-1 axis

in-vitro,

OS,

TumCP↓, Ferroptosis↓, Hif1a↑, HO-1↑, Iron↑, ROS↑, GSH/GSSG↓, GPx4↓,

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,

(20μg/dose/day)

mice

tumCV↓, TumCCA↑, Apoptosis↑, EGFR↓, PI3K↓, Hif1a↓, PKM2↓, cycD1/CCND1↓, AntiTum↑,

Showing Research Papers: 51 to 100 of 105
Prev Page 2 of 3 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 105

Pathway results for Effect on Cancer / Diseased Cells:

Functional Outcomes ⓘ

AntiTum↑, 1, TumVol↓, 2, TumW↓, 2,
Total Targets: 175

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, CYP1A1↑, 1, Ferroptosis↓, 1, GPx4↓, 1, GSH↑, 2, HO-1↑, 3, HO-1↝, 1, Iron↓, 1, lipid-P↑, 1, MDA↓, 1, MPO↓, 1, NQO1↑, 2, NRF2↓, 1, NRF2↑, 7, ROS↓, 5, SOD↑, 3,

Metal & Cofactor Biology ⓘ

NCOA4↝, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 2, AMPK↑, 1, CYP2C6↑, 1, CYP3A2↑, 1, SIRT1↑, 1,

Cell Death ⓘ

AhR↑, 1, Apoptosis↓, 2, BAX↓, 1, Bcl-2↑, 1, Casp12↓, 1, Casp3↓, 1, cl‑Casp3↓, 1, Ferroptosis↓, 1, iNOS↓, 1, p‑p38↓, 1,

Transcription & Epigenetics ⓘ

p‑cJun↓, 1,

Protein Folding & ER Stress ⓘ

CHOP↓, 1, ER Stress↓, 1, GRP78/BiP↓, 1,

Proliferation, Differentiation & Cell State ⓘ

EMT↑, 1, p‑ERK↓, 1, Mst1↓, 1,

Migration ⓘ

ARG↑, 1, CYP2D1↑, 1, E-sel↓, 1, TGF-β↑, 1, VCAM-1↓, 1,

Immune & Inflammatory Signaling ⓘ

ICAM-1↓, 1, IL10↓, 1, IL10↑, 1, IL17↓, 2, IL1β↓, 2, IL6↓, 4, IL8↓, 1, Inflam?, 1, Inflam↓, 5, NF-kB↓, 1, p‑NF-kB↓, 1, p‑p50↓, 1, p‑p65↓, 1, TNF-α↓, 5,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, CYP1A2↑, 1, Dose↝, 1, eff↓, 3, eff↑, 1,

Clinical Biomarkers ⓘ

ALAT↓, 2, AST↓, 2, BMD↑, 1, IL6↓, 4,

Functional Outcomes ⓘ

cardioP↑, 1, hepatoP↑, 2, neuroP↑, 2, RenoP↑, 2, toxicity↓, 3, toxicity∅, 1,
Total Targets: 73

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#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Shikonin Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Cellular Microenvironment ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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