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⟱

2232-

SK,

Shikonin Induces Autophagy and Apoptosis in Esophageal Cancer EC9706 Cells by Regulating the AMPK/mTOR/ULK Axis

in-vitro,

ESCC,

EC9706

2.26 ± 0.12 µM

"highlight2" >tumCV↓, "highlight2" >TumCMig↓, "highlight2" >TumCI↓, "highlight2" >TumAuto↑, "highlight2" >Apoptosis↑, "highlight2" >Bcl-2↓, "highlight2" >BAX↑, "highlight2" >cl‑Casp3↑, "highlight2" >cl‑Casp8↑, "highlight2" >cl‑PARP↑, "highlight2" >AMPK↑, "highlight2" >mTOR↑, "highlight2" >TumVol↓, "highlight2" >OS↑, "highlight2" >LC3I↑,

2364-

SK,

Pyruvate Kinase M2 Mediates Glycolysis Contributes to Psoriasis by Promoting Keratinocyte Proliferation

in-vivo,

PSA,

For 2-DG or Shikonin treatment, mice were intraperitoneally injected with 2-DG (500 mg/kg in saline, daily for 5 days) or Shikonin (25 mg/kg in saline/1% DMSO. daily for 5 days).

mice

"highlight2" >eff↑, "highlight2" >lactateProd↓, "highlight2" >PKM2↓,

2363-

SK,

Inhibition of PKM2 by shikonin impedes TGF-β1 expression by repressing histone lactylation to alleviate renal fibrosis

in-vivo,

CKD,

mice

"highlight2" >PKM2↓, "highlight2" >lactateProd↓, "highlight2" >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,

Rat C6 tumor xenograft in nude mice

in-vitro,

GBM,

U251

"highlight2" >RIP1↑, "highlight2" >RIP3↑, "highlight2" >Glycolysis↓, "highlight2" >G6PD↓, "highlight2" >HK2↓, "highlight2" >PKM2↓, "highlight2" >H2O2↑, "highlight2" >GSH↓, "highlight2" >ROS↑,

2361-

SK,

Natural shikonin and acetyl-shikonin improve intestinal microbial and protein composition to alleviate colitis-associated colorectal cancer

in-vivo,

CRC,

mice

"highlight2" >GutMicro↑, "highlight2" >Dose↝, "highlight2" >IL1β↓, "highlight2" >IL6↓, "highlight2" >TNF-α↓, "highlight2" >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

4 or 8 umol/L

in-vitro,

NPC,

SUNE-1

"highlight2" >TumCP↓, "highlight2" >Apoptosis↑, "highlight2" >TumCMig↓, "highlight2" >TumCI↓, "highlight2" >GlucoseCon↓, "highlight2" >lactateProd↓, "highlight2" >ATP↓, "highlight2" >PKM2↓, "highlight2" >PI3K↓, "highlight2" >Akt↓, "highlight2" >MMP3↓, "highlight2" >MMP9↓, "highlight2" >TIMP1↑,

2359-

SK,

Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery

in-vivo,

Liver,

mice

"highlight2" >TumCG↓, "highlight2" >PKM2↓, "highlight2" >EMT↓, "highlight2" >TGF-β↓, "highlight2" >Glycolysis↓, "highlight2" >lactateProd↓, "highlight2" >ATP↓,

2358-

SK,

SIRT1 improves lactate homeostasis in the brain to alleviate parkinsonism via deacetylation and inhibition of PKM2

in-vivo,

Park,

mice

"highlight2" >*eff↑, "highlight2" >*PKM2↓, "highlight2" >*motorD↑, "highlight2" >*lactateProd↓,

2357-

SK,

GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism

Study,

HCC,

182 patients with HCC undergoing curative hepatectomy

in-vivo,

NA,

mouse

"highlight2" >AntiTum↑, "highlight2" >GTPBP4↓, "highlight2" >PKM2↓, "highlight2" >lactateProd↓, "highlight2" >GlucoseCon↓, "highlight2" >Glycolysis↓, "highlight2" >E-cadherin↑, "highlight2" >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,

(1 mg/kg) by intraperitoneal injection once every 3 days

mice

"highlight2" >PKM2↓, "highlight2" >Glycolysis↓, "highlight2" >FASN↓, "highlight2" >lactateProd↓, "highlight2" >Warburg↓, "highlight2" >TumCG↓, "highlight2" >VM↓,

2355-

SK,

Pharmacological properties and derivatives of shikonin-A review in recent years

Review,

Var,

"highlight2" >AntiCan↑, "highlight2" >TumCP↓, "highlight2" >TumCMig↓, "highlight2" >Apoptosis↑, "highlight2" >TumAuto↑, "highlight2" >Necroptosis↑, "highlight2" >ROS↑, "highlight2" >TrxR1↓, "highlight2" >PKM2↓, "highlight2" >RIP1↓, "highlight2" >RIP3↓, "highlight2" >Src↓, "highlight2" >FAK↓, "highlight2" >PI3K↓, "highlight2" >Akt↓, "highlight2" >mTOR↓, "highlight2" >GRP58↓, "highlight2" >MMPs↓, "highlight2" >ATF2↓, "highlight2" >cl‑PARP↑, "highlight2" >Casp3↑, "highlight2" >p‑p38↑, "highlight2" >p‑JNK↑, "highlight2" >p‑ERK↓,

2354-

SK,

PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation

in-vivo,

Sepsis,

mice

"highlight2" >PKM2↓, "highlight2" >*PKM2↓, "highlight2" >*IL1β↓, "highlight2" >*IL18↓, "highlight2" >*HMGB1↓, "highlight2" >*Casp1↓, "highlight2" >*NLRP3↓, "highlight2" >*AIM2↓, "highlight2" >*p‑eIF2α↓, "highlight2" >*Sepsis↓,

2234-

SK,

Shikonin Suppresses Cell Tumorigenesis in Gastric Cancer Associated with the Inhibition of c-Myc and Yap-1

in-vitro,

GC,

"highlight2" >TumCP↓, "highlight2" >TumCI↓, "highlight2" >TumCMig↓, "highlight2" >cMyc↓, "highlight2" >YAP/TEAD↓,

2233-

SK,

Clinical trial on the effects of shikonin mixture on later stage lung cancer

Trial,

Lung,

19 cases of later-stage lung cancer

"highlight2" >TumVol↓, "highlight2" >Remission↑, "highlight2" >OS↑, "highlight2" >QoL↑, "highlight2" >Weight↑, "highlight2" >*toxicity∅,

2370-

SK,

The role of pyruvate kinase M2 in anticancer therapeutic treatments

Review,

Var,

"highlight2" >Glycolysis↓, "highlight2" >PKM2↓, "highlight2" >EGFR↓, "highlight2" >PI3K↓, "highlight2" >p‑Akt↓, "highlight2" >Hif1a↓,

2231-

SK,

Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways

in-vitro,

CRC,

SNU-407

3 µM after 48 h

"highlight2" >Apoptosis↑, "highlight2" >ER Stress↑, "highlight2" >PERK↑, "highlight2" >eIF2α↑, "highlight2" >CHOP↑, "highlight2" >mt-Ca+2↑, "highlight2" >MMP↓, "highlight2" >Bcl-2↓, "highlight2" >Casp3↑, "highlight2" >Casp9↑, "highlight2" >ERK↑, "highlight2" >JNK↑, "highlight2" >p38↓,

2230-

SK,

Shikonin induces ROS-based mitochondria-mediated apoptosis in colon cancer

in-vitro,

CRC,

HCT116

in-vivo,

NA,

"highlight2" >TumCG↓, "highlight2" >Bcl-2↓, "highlight2" >ROS↑, "highlight2" >Bcl-xL↓, "highlight2" >MMP↓, "highlight2" >Casp↑, "highlight2" >selectivity↑, "highlight2" >cycD1/CCND1↓, "highlight2" >TumCCA↑, "highlight2" >eff↓,

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

"highlight2" >Apoptosis↑, "highlight2" >TumAuto↑, "highlight2" >TumCP↓, "highlight2" >TumCCA↑, "highlight2" >P21↑, "highlight2" >cycD1/CCND1↓, "highlight2" >ER Stress↑, "highlight2" >p‑eIF2α↑, "highlight2" >CHOP↑, "highlight2" >cl‑Casp3↑, "highlight2" >p38↑, "highlight2" >LC3B-II↑, "highlight2" >Beclin-1↑, "highlight2" >ROS↑, "highlight2" >eff↓,

2228-

SK,

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

in-vitro,

CRC,

HCT116

0.25, 0.5, 1, 1.5, 2, 2.5 and 3 μM

in-vitro,

CRC,

HCT15

in-vivo,

NA,

 intraperitoneal injection (3 mg/kg, 3 times per week

mouse

"highlight2" >Apoptosis↑, "highlight2" >Bcl-2↓, "highlight2" >Casp3↑, "highlight2" >Casp9↑, "highlight2" >cl‑PARP↑, "highlight2" >GRP78/BiP↑, "highlight2" >PERK↑, "highlight2" >eIF2α↑, "highlight2" >ATF4↑, "highlight2" >CHOP↑, "highlight2" >JNK↑, "highlight2" >eff↓, "highlight2" >ER Stress↑, "highlight2" >ROS↑, "highlight2" >TumCG↓,

2227-

SK,

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

in-vitro,

GC,

BGC-823

13.35uM

in-vitro,

GC,

SGC-7901

9.63uM

in-vitro,

Nor,

GES-1

>20 μM

"highlight2" >selectivity↑, "highlight2" >TumCP↓, "highlight2" >TumCD↑, "highlight2" >ROS↑, "highlight2" >MMP↓, "highlight2" >Casp↑, "highlight2" >Cyt‑c↑, "highlight2" >Endon↑, "highlight2" >AIF↑, "highlight2" >eff↓, "highlight2" >ChemoSen↑, "highlight2" >TumCCA↑, "highlight2" >GSH/GSSG↓, "highlight2" >lipid-P↑,

2226-

SK,

Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma

in-vitro,

HCC,

HUH7

in-vitro,

HCC,

Bel-7402

"highlight2" >selectivity↑, "highlight2" >ROS↑, "highlight2" >eff↓, "highlight2" >Akt↓, "highlight2" >RIP1↓, "highlight2" >NF-kB↓,

2225-

SK,

Shikonin protects skin cells against oxidative stress and cellular dysfunction induced by fine particulate matter

in-vitro,

Nor,

HaCaT

"highlight2" >*antiOx↑, "highlight2" >*ROS↓, "highlight2" >*GSH↑, "highlight2" >*GCLC↑, "highlight2" >*GSS↑, "highlight2" >*Akt↑, "highlight2" >*NRF2↑,

2224-

SK,

Shikonin induces apoptosis and autophagy via downregulation of pyrroline-5-carboxylate reductase1 in hepatocellular carcinoma cells

in-vitro,

HCC,

SMMC-7721 cell

in-vitro,

HCC,

HUH7

in-vitro,

HCC,

HepG2

"highlight2" >PYCR1↓, "highlight2" >PI3K↓, "highlight2" >Akt↓, "highlight2" >mTOR↓, "highlight2" >eff↑,

2223-

SK,

Non-metabolic enzyme function of PKM2 in hepatocellular carcinoma: A review

in-vitro,

Var,

"highlight2" >PKM2↓,

2222-

SK,

The anti-tumor effect of shikonin on osteosarcoma by inducing RIP1 and RIP3 dependent necroptosis

in-vitro,

OS,

U2OS

in-vitro,

OS,

143B

in-vivo,

NA,

mice

"highlight2" >Necroptosis↑, "highlight2" >RIP1↑, "highlight2" >RIP3↑, "highlight2" >OS↑, "highlight2" >P53↑,

2221-

SK,

Shikonin Induces Apoptosis, Necrosis, and Premature Senescence of Human A549 Lung Cancer Cells through Upregulation of p53 Expression

in-vitro,

Lung,

A549

0.5, 1.0, 2.5, 5.0, or 10.0 μg/mL)

3.52ug/mL

"highlight2" >Apoptosis↑, "highlight2" >TumCP↓, "highlight2" >tumCV↓, "highlight2" >Necroptosis↑, "highlight2" >P53↑, "highlight2" >ROS↑, "highlight2" >NF-kB↓,

2220-

SK,

Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades

in-vivo,

Nor,

Nine-week-old Wistar rats were administered 6.25, 12.5, and 25 mg/kg/day shikonin orally, one hour after the i.p. injection of 100 mg/kg/day gentamicin for seven days

"highlight2" >*RenoP↑, "highlight2" >*ROS↓, "highlight2" >*SIRT1↓, "highlight2" >*NRF2↑, "highlight2" >*HO-1↑, "highlight2" >*GSH↑, "highlight2" >*TAC↑, "highlight2" >*SOD↑, "highlight2" >*MDA↓, "highlight2" >*NO↓, "highlight2" >*iNOS↓, "highlight2" >*NHE3↑, "highlight2" >*PI3K↑,

3044-

SK,

Shikonin Inhibits Non-Small-Cell Lung Cancer H1299 Cell Growth through Survivin Signaling Pathway

in-vitro,

Lung,

H1299

in-vitro,

Lung,

H460

"highlight2" >TumCP↓, "highlight2" >survivin↓, "highlight2" >TumCCA↓, "highlight2" >CDK2↓, "highlight2" >CDK4↓, "highlight2" >XIAP↓, "highlight2" >Casp3↑, "highlight2" >Casp9↑, "highlight2" >cycD1/CCND1↓, "highlight2" >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

12.5-100 ng/mL dosage of shikonin treatment on AGS cancer cell

"highlight2" >TumCP↓, "highlight2" >TumCCA↑, "highlight2" >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

"highlight2" >CSCs↓, "highlight2" >TumCP↓, "highlight2" >Nanog↓, "highlight2" >OCT4↓, "highlight2" >p‑Akt↓, "highlight2" >P70S6K↓, "highlight2" >PI3K↓, "highlight2" >mTOR↓, "highlight2" >eff↑,

5102-

SK,

GEM,

Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-κB signaling pathway

"highlight2" >TumCG↓, "highlight2" >ChemoSen↑, "highlight2" >NF-kB↓, "highlight2" >PCNA↓, "highlight2" >Ki-67↓, "highlight2" >p‑EGFR↓, "highlight2" >ROS↑, "highlight2" >TumCCA↑, "highlight2" >P53↑, "highlight2" >JNK↑, "highlight2" >Akt↓,

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

"highlight2" >Apoptosis↑, "highlight2" >TumAuto↑, "highlight2" >Gal1↑, "highlight2" >TumCP↓, "highlight2" >ROS↑, "highlight2" >eff↑,

5100-

SK,

Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expression

vitro+vivo,

NPC,

"highlight2" >TumCP↓, "highlight2" >RIP1↑, "highlight2" >ROS↑, "highlight2" >Necroptosis↑, "highlight2" >Casp3↑, "highlight2" >Casp8↑, "highlight2" >eff↓, "highlight2" >TumCG↓,

3051-

SK,

Resveratrol mediates its anti-cancer effects by Nrf2 signaling pathway activation

Review,

Var,

"highlight2" >Nrf1↑, "highlight2" >Apoptosis↑, "highlight2" >TumCP↓, "highlight2" >eff⇅, "highlight2" >chemoP↑, "highlight2" >eff↑, "highlight2" >VCAM-1↓, "highlight2" >Hif1a↓,

3050-

SK,

Systemic administration of Shikonin ameliorates cognitive impairment and neuron damage in NPSLE mice

in-vivo,

Nor,

mice

"highlight2" >*Inflam↓, "highlight2" >*neuroP↑, "highlight2" >*cognitive↑,

3049-

SK,

Shikonin Attenuates Chronic Cerebral Hypoperfusion-Induced Cognitive Impairment by Inhibiting Apoptosis via PTEN/Akt/CREB/BDNF Signaling

in-vivo,

Nor,

Fifty-two rats

NA,

Stroke,

"highlight2" >*neuroP↑, "highlight2" >*p‑PTEN↓, "highlight2" >*p‑Akt↑, "highlight2" >*Bcl-2↑, "highlight2" >*BAX↓, "highlight2" >*cognitive↑, "highlight2" >*BDNF↑,

3048-

SK,

Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3β-regulated suppression of β-catenin signaling

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

4T1

in-vitro,

Nor,

MCF12A

in-vivo,

NA,

"highlight2" >tumCV↓, "highlight2" >selectivity↑, "highlight2" >EMT↓, "highlight2" >TumCMig↓, "highlight2" >TumCI↓, "highlight2" >E-cadherin↑, "highlight2" >N-cadherin↓, "highlight2" >Vim↓, "highlight2" >Snail↓, "highlight2" >β-catenin/ZEB1↓, "highlight2" >GSK‐3β↑,

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

"highlight2" >TumCG↓, "highlight2" >p‑STAT3↓, "highlight2" >ADAM17↓, "highlight2" >Apoptosis↑, "highlight2" >Casp3↑, "highlight2" >cl‑PARP↑, "highlight2" >cycD1/CCND1↓, "highlight2" >cycE/CCNE↓, "highlight2" >TumCCA↑, "highlight2" >JAK1?, "highlight2" >p‑JAK1↓, "highlight2" >p‑JAK2↓, "highlight2" >p‑eIF2α↑, "highlight2" >eff↓, "highlight2" >ROS↑, "highlight2" >IL6↓,

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

"highlight2" >TumCP↓, "highlight2" >TumCI↓, "highlight2" >TumCMig↓, "highlight2" >p‑ERK↓, "highlight2" >ITGB1↓,

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

"highlight2" >ECAR↓, "highlight2" >Glycolysis↓, "highlight2" >ATP↓, "highlight2" >PKM2↓, "highlight2" >TumCMig↓, "highlight2" >Ca+2↑, "highlight2" >GlucoseCon↓, "highlight2" >lactateProd↓, "highlight2" >MMP↓, "highlight2" >ROS↑,

2219-

SK,

Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways

in-vitro,

Nor,

HaCaT

 (0–4 µM) for 24 and 48 h

6.34uM@24h

"highlight2" >*MMP↓, "highlight2" >*ROS↑, "highlight2" >*Casp3↑, "highlight2" >*TumCG↓,

3043-

SK,

Shikonin Induces Apoptosis by Inhibiting Phosphorylation of IGF-1 Receptor in Myeloma Cells.

in-vitro,

Melanoma,

RPMI-8226

"highlight2" >IGF-1↓, "highlight2" >Apoptosis↑, "highlight2" >TumCCA↑, "highlight2" >MMP↓, "highlight2" >Casp3↑, "highlight2" >P53↑, "highlight2" >BAX↑, "highlight2" >Mcl-1↓, "highlight2" >EGFR↓, "highlight2" >Src↑, "highlight2" >KDR/FLK-1↓, "highlight2" >p‑IGF-1↓, "highlight2" >PI3K↓, "highlight2" >Akt↓,

3042-

SK,

The protective effects of Shikonin on lipopolysaccharide/D -galactosamine-induced acute liver injury via inhibiting MAPK and NF-kB and activating Nrf2/HO-1 signaling pathways

in-vivo,

Nor,

mice

"highlight2" >*TNF-α↓, "highlight2" >*IL1β↓, "highlight2" >*IL6↓, "highlight2" >*IFN-γ↓, "highlight2" >*ALAT↓, "highlight2" >*AST↓, "highlight2" >*MPO↓, "highlight2" >*ROS↓, "highlight2" >*JNK↓, "highlight2" >*ERK↓, "highlight2" >*p38↓, "highlight2" >*NF-kB↓, "highlight2" >*p‑IKKα↓, "highlight2" >*SOD↑, "highlight2" >*GSH↑, "highlight2" >*HO-1↑, "highlight2" >*NRF2↑, "highlight2" >*hepatoP↑,

3041-

SK,

Promising Nanomedicines of Shikonin for Cancer Therapy

Review,

Var,

"highlight2" >Glycolysis↓, "highlight2" >TAMS↝, "highlight2" >BioAv↓, "highlight2" >Half-Life↝, "highlight2" >P21↑, "highlight2" >ERK↓, "highlight2" >ROS↑, "highlight2" >GSH↓, "highlight2" >MMP↓, "highlight2" >TrxR↓, "highlight2" >MMP13↓, "highlight2" >MMP2↓, "highlight2" >MMP9↓, "highlight2" >SIRT2↑, "highlight2" >Hif1a↓, "highlight2" >PKM2↓, "highlight2" >TumCP↓, "highlight2" >TumMeta↓,

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

Pathway results for Effect on Normal Cells:

Infection & Microbiome ⓘ

Sepsis↓, 1,
Total Targets: 65

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 Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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