Silymarin (Milk Thistle) silibinin / ERK Cancer Research Results

SIL, Silymarin (Milk Thistle) silibinin: Click to Expand ⟱
Features:
Silymarin (Milk Thistle) Flowering herb related to daisy and ragweed family.
Silibinin (INN), also known as silybin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds.
-a flavonoid combination of 65–80% of seven flavolignans; the most important of these include silybin, isosilybin, silychristin, isosilychristin, and silydianin. Silybin is the most abundant compound in around 50–70% in isoforms silybin A and silybin B

-Note half-life 6hrs?.
BioAv not soluble in water, low bioAv (1%). 240mg yielded only 0.34ug/ml plasma level. oral administration of SM (equivalent to 120 mg silibinin), total (unconjugated + conjugated) silibinin concentration in plasma was 1.1–1.3 μg/mL, so can not achieve levels used in most in-vitro studies.
Pathways:
- results for both inducing and reducing ROS in cancer cells. In normal cell seems to consistently lower ROS. Reports show both ROS↑ and ROS↓ in cancer models; systemic pro-oxidant effects may require higher exposures than typical oral dosing, but local or combination contexts may differ. (level in GUT could be much higher (800uM).
- ROS↑ related: MMP↓(ΔΨm), Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑,
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, p38↓(context-dependent; often stress-activated), Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, uPA↓, VEGF↓, FAK↓, NF-κB↓, CXCR4↓, TGF-β↓, α-SMA↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, DNMTs↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, GRP78↑(ER stress), Glucose↓, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, PDGF↓, EGFR↓,
- inhibits Cancer Stem Cells : CSC↓, Hh↓, GLi1↓, β-catenin↓, Notch2↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, - SREBP (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS / redox buffering + mitochondrial protection Often ↑ stress susceptibility; can support apoptosis when survival signaling is blocked ↓ oxidative stress; mitochondrial protection P, R, G Context-selective redox modulation Silymarin is classically cytoprotective/antioxidant in normal tissues (notably liver), while in tumors it can weaken pro-survival adaptation and increase vulnerability to stressors and therapy.
2 Intrinsic apoptosis (mitochondria → caspases) ↑ apoptosis signaling; ↑ caspase activation ↔ minimal activation G Cell death execution Common downstream outcome in cancer models: apoptosis increases after earlier signaling/redox shifts and/or checkpoint disruption.
3 Cell-cycle control (cyclins/CDKs; checkpoints) ↑ arrest (G1/S or G2/M depending on model) ↔ G Cytostasis Typically observed as reduced proliferation with checkpoint engagement; timing usually later than kinase phosphorylation changes.
4 NF-κB inflammatory transcription ↓ NF-κB activity; ↓ inflammatory/pro-survival tone ↔ or protective anti-inflammatory effect R, G Anti-inflammatory / anti-survival transcription NF-κB suppression can reduce tumor-promoting inflammation and blunt stress-adaptive survival programs.
5 JAK/STAT3 axis (incl. PD-L1 / immune escape programs in some models) ↓ STAT3 signaling (context); may ↓ PD-L1 in certain tumor contexts ↔ R, G Reduced survival + immune-evasion signaling Reported to attenuate STAT3-driven tumor programs and, in some contexts, reduce immune-suppressive signaling (model dependent).
6 PI3K → AKT → mTOR survival / growth signaling ↓ PI3K/AKT/mTOR signaling (context) ↔ R, G Growth/survival suppression Reduced PI3K/AKT/mTOR tone increases sensitivity to apoptosis and can reinforce cell-cycle arrest.
7 MAPK re-wiring (ERK/p38/JNK balance) Stress-MAPK shifts; ERK tone often reduced or re-patterned ↔ P, R, G Signal reprogramming Early phosphorylation shifts can precede later gene-expression changes; exact ERK direction is model and dose dependent.
8 Angiogenesis (VEGF and angiogenic factors) ↓ VEGF / angiogenesis outputs ↔ G Anti-angiogenic support Typically reflected in reduced pro-angiogenic expression/secretion and angiogenesis-related phenotypes over longer windows.
9 EMT / invasion / migration programs (incl. TGF-β/Smad-associated EMT in some systems) ↓ EMT markers; ↓ migration/invasion ↔ G Anti-invasive phenotype Often presents as restoration of epithelial markers and suppression of migration/invasion assays; commonly a later phenotype-level outcome.
10 Xenobiotic handling (Phase I/II enzymes; cytoprotection / chemoprevention framing) May alter carcinogen activation/detox balance ↑ detox / cytoprotection against xenobiotics G Chemopreventive protection A key “dual strategy” theme: protection of normal tissue from toxins/therapy while modulating tumor response pathways.
11 Drug resistance / efflux (MDR phenotype; P-gp-related resistance in some models) May ↓ functional MDR and ↑ chemo sensitivity (context) ↔ R, G Chemo-sensitization support Reported synergy with chemotherapy in resistant tumor settings; transporter direction can be context-specific, so present as “reported to reduce functional resistance” rather than a universal single-transporter claim.
12 Immune microenvironment signaling (cytokines / macrophage recruitment in some models) May ↓ pro-tumor cytokine programs and recruitment signals (context) ↔ G Anti-inflammatory tumor microenvironment shift Immune-modulatory effects are increasingly discussed, but they are more model-dependent and typically show on longer time scales.

Time-Scale Flag (TSF): P / R / G

  • P: 0–30 min (primary/physical–chemical effects; rapid signaling / phosphorylation shifts)
  • R: 30 min–3 hr (redox signaling + acute stress-response signaling)
  • G: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)
ERK, ERK signaling: Click to Expand ⟱
Source:
Type:
MAPK3 (ERK1)
ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.
The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior

EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.
Scientific Papers found: Click to Expand⟱
3331- SIL,    The clinical anti-inflammatory effects and underlying mechanisms of silymarin
- Review, NA, NA
*Inflam↓, *NF-kB↓, *NLRP3↓, *COX2↓, *iNOS↓, *neuroP↑, *p‑ERK↓, *p38↓, *MAPK↓, *EGFR↓, *ROS↓, *lipid-P?, *5LO↓,
3319- SIL,    Silymarin and neurodegenerative diseases: Therapeutic potential and basic molecular mechanisms
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*neuroP↑, *ROS↓, *Inflam↓, *Apoptosis↓, *BBB?, *tau↓, *NF-kB↓, *IL1β↓, *TNF-α↓, *IL4↓, *MAPK↓, *memory↑, *cognitive↑, *Aβ↓, *ROS↓, *lipid-P↓, *GSH↑, *MDA↓, *SOD↑, *Catalase↑, *AChE↓, *BChE↓, *p‑ERK↓, *p‑JNK↓, *p‑p38↓, *GutMicro↑, *COX2↓, *iNOS↓, *TLR4↓, *neuroP↑, *Strength↑, *AMPK↑, *MMP↑, *necrosis↓, *NRF2↑, *HO-1↑,
3288- SIL,    Silymarin in cancer therapy: Mechanisms of action, protective roles in chemotherapy-induced toxicity, and nanoformulations
- Review, Var, NA
Inflam↓, lipid-P↓, TumMeta↓, angioG↓, chemoP↑, EMT↓, HDAC↓, HATs↑, MMPs↓, uPA↓, PI3K↓, Akt↓, VEGF↓, CD31↓, Hif1a↓, VEGFR2↓, Raf↓, MEK↓, ERK↓, BIM↓, BAX↑, Bcl-2↓, Bcl-xL↓, Casp↑, MAPK↓, P53↑, LC3II↑, mTOR↓, YAP/TEAD↓, *BioAv↓, MMP↓, Cyt‑c↑, PCNA↓, cMyc↓, cycD1/CCND1↓, β-catenin/ZEB1↓, survivin↓, APAF1↑, Casp3↑, MDSCs↓, IL10↓, IL2↑, IFN-γ↑, hepatoP↑, cardioP↑, GSH↑, neuroP↑,
3295- SIL,    Hepatoprotective effect of silymarin
- Review, NA, NA
*hepatoP↑, *ROS↓, *GSH↑, *BioAv↝, ERK↓, NF-kB↓, STAT3↓, COX2↓, Inflam↓, IronCh↑, lipid-P↓, ALAT↓, AST↓, TNF-α↓, *α-SMA↓, *SOD↑,
3293- SIL,    Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer
- Review, Var, NA
hepatoP↑, TumMeta↓, Inflam↓, chemoP↑, radioP↑, Half-Life↝, *GSTs↑, p‑JNK↑, BAX↑, p‑p38↑, cl‑PARP↑, Bcl-2↓, p‑ERK↓, TumVol↓, eff↑, TumCCA↑, STAT3↓, Mcl-1↓, survivin↓, Bcl-xL↓, Casp3↑, Casp9↑, eff↑, CXCR4↓, Dose↝,
3290- SIL,    A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents
- Analysis, Var, NA
hepatoP↑, chemoP↑, *lipid-P↓, *antiOx↑, tumCV↓, TumCMig↓, Apoptosis↑, ROS↑, GSH↓, Bcl-2↓, survivin↓, cycD1/CCND1↓, NOTCH1↓, BAX↑, NF-kB↓, COX2↓, LOX1↓, iNOS↓, TNF-α↓, IL1↓, Inflam↓, *toxicity↓, CXCR4↓, EGFR↓, ERK↓, MMP↓, Cyt‑c↑, TumCCA↑, RB1↑, P53↑, P21↑, p27↑, cycE/CCNE↓, CDK4↓, p‑pRB↓, Hif1a↓, cMyc↓, IL1β↓, IFN-γ↓, PCNA↓, PSA↓, CYP1A1↓,
3282- SIL,    Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions
- Review, NA, NA
hepatoP↑, AntiCan↑, TumCMig↓, Hif1a↓, selectivity↑, toxicity∅, *antiOx↑, *Inflam↓, TumCCA↑, P21↑, CDK4↓, NF-kB↓, ERK↓, PSA↓, TumCG↓, p27↑, COX2↓, IL1↓, VEGF↓, IGFBP3↑, AR↓, STAT3↓, Telomerase↓, Cyt‑c↑, Casp↑, eff↝, HDAC↓, HATs↑, Zeb1↓, E-cadherin↑, miR-203↑, NHE1↓, MMP2↓, MMP9↓, PGE2↓, Vim↓, Wnt↓, angioG↓, VEGF↓, *TIMP1↓, EMT↓, TGF-β↓, CD44↓, EGFR↓, PDGF↓, *IL8↓, SREBP1↓, MMP↓, ATP↓, uPA↓, PD-L1↓, NOTCH↓, *SIRT1↑, SIRT1↓, CA↓, Ca+2↑, chemoP↑, cardioP↑, Dose↝, Half-Life↝, BioAv↓, BioAv↓, BioAv↓, toxicity↝, Half-Life↓, ROS↓, FAK↓,
978- SIL,    A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment
- Review, NA, NA
PI3K↓, Akt↓, NF-kB↓, Wnt/(β-catenin)↓, MAPK↓, TumCP↓, TumCCA↑, Apoptosis↑, p‑EGFR↓, JAK2↓, STAT5↓, cycD1/CCND1↓, hTERT/TERT↓, AP-1↓, MMP9↓, miR-21↓, miR-155↓, Casp9↑, BID↑, ERK↓, Akt2↓, DNMT1↓, P53↑, survivin↓, Casp3↑, ROS↑,
1276- SIL,    Silibinin inhibits TPA-induced cell migration and MMP-9 expression in thyroid and breast cancer cells
- in-vitro, BC, NA - in-vitro, Thyroid, NA
TumCMig↓, MMP9↓, p‑MEK↓, p‑ERK↓,
3305- SIL,    Silymarin inhibits proliferation of human breast cancer cells via regulation of the MAPK signaling pathway and induction of apoptosis
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vivo, NA, NA
TumCP↓, tumCV↓, BAX↑, cl‑PARP↑, Casp9↑, p‑JNK↑, Bcl-2↓, p‑p38↓, p‑ERK↓, *toxicity∅, Dose↝, *hepatoP↑, Inflam↓, AntiCan↑,
3304- SIL,    Silymarin induces inhibition of growth and apoptosis through modulation of the MAPK signaling pathway in AGS human gastric cancer cells
- in-vitro, GC, AGS - in-vivo, NA, NA
BAX↑, p‑JNK↑, p‑p38↑, cl‑PARP↑, Bcl-2↓, p‑ERK↓, TumVol↓, Apoptosis↑, tumCV↓,
3301- SIL,    Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid
- Review, Var, NA
Inflam↓, TumCCA↑, Apoptosis↓, TumMeta↓, TumCG↓, angioG↓, chemoP↑, radioP↑, p‑ERK↓, p‑p38↓, p‑JNK↓, P53↑, Bcl-2↓, Bcl-xL↓, TGF-β↓, MMP2↓, MMP9↓, E-cadherin↑, Wnt↓, Vim↓, VEGF↓, IL6↓, STAT3↓, *ROS↓, IL1β↓, PGE2↓, CDK1↓, CycB/CCNB1↓, survivin↓, Mcl-1↓, Casp3↑, Casp9↑, cMyc↓, COX2↓, Hif1a↓, CXCR4↓, CSCs↓, EMT↓, N-cadherin↓, PCNA↓, cycD1/CCND1↓, ROS↑, eff↑, eff↑, eff↑, HER2/EBBR2↓,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

CYP1A1↓, 1,   GSH↓, 1,   GSH↑, 1,   lipid-P↓, 2,   ROS↓, 1,   ROS↑, 3,  

Metal & Cofactor Biology ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MEK↓, 1,   p‑MEK↓, 1,   MMP↓, 3,   Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   cMyc↓, 3,   SIRT1↓, 1,   SREBP1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   APAF1↑, 1,   Apoptosis↓, 1,   Apoptosis↑, 3,   BAX↑, 5,   Bcl-2↓, 6,   Bcl-xL↓, 3,   BID↑, 1,   BIM↓, 1,   Casp↑, 2,   Casp3↑, 4,   Casp9↑, 4,   Cyt‑c↑, 3,   hTERT/TERT↓, 1,   iNOS↓, 1,   p‑JNK↓, 1,   p‑JNK↑, 3,   MAPK↓, 2,   Mcl-1↓, 2,   p27↑, 2,   p‑p38↓, 2,   p‑p38↑, 2,   survivin↓, 5,   Telomerase↓, 1,   YAP/TEAD↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

HATs↑, 2,   miR-21↓, 1,   p‑pRB↓, 1,   tumCV↓, 3,  

Autophagy & Lysosomes ⓘ

LC3II↑, 1,  

DNA Damage & Repair ⓘ

DNMT1↓, 1,   P53↑, 4,   cl‑PARP↑, 3,   PCNA↓, 3,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK4↓, 2,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 4,   cycE/CCNE↓, 1,   P21↑, 2,   RB1↑, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

CD44↓, 1,   CSCs↓, 1,   EMT↓, 3,   ERK↓, 5,   p‑ERK↓, 5,   HDAC↓, 2,   IGFBP3↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   NOTCH1↓, 1,   PI3K↓, 2,   STAT3↓, 4,   STAT5↓, 1,   TumCG↓, 2,   Wnt↓, 2,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

Akt2↓, 1,   AP-1↓, 1,   CA↓, 1,   Ca+2↑, 1,   CD31↓, 1,   E-cadherin↑, 2,   FAK↓, 1,   miR-155↓, 1,   miR-203↑, 1,   MMP2↓, 2,   MMP9↓, 4,   MMPs↓, 1,   N-cadherin↓, 1,   PDGF↓, 1,   TGF-β↓, 2,   TumCMig↓, 3,   TumCP↓, 2,   TumMeta↓, 3,   uPA↓, 2,   Vim↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   EGFR↓, 2,   p‑EGFR↓, 1,   Hif1a↓, 4,   LOX1↓, 1,   VEGF↓, 4,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

NHE1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   CXCR4↓, 3,   IFN-γ↓, 1,   IFN-γ↑, 1,   IL1↓, 2,   IL10↓, 1,   IL1β↓, 2,   IL2↑, 1,   IL6↓, 1,   Inflam↓, 6,   JAK2↓, 1,   MDSCs↓, 1,   NF-kB↓, 4,   PD-L1↓, 1,   PGE2↓, 2,   PSA↓, 2,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   Dose↝, 3,   eff↑, 5,   eff↝, 1,   Half-Life↓, 1,   Half-Life↝, 2,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   AR↓, 1,   AST↓, 1,   EGFR↓, 2,   p‑EGFR↓, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 1,   IL6↓, 1,   PD-L1↓, 1,   PSA↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 2,   cardioP↑, 2,   chemoP↑, 5,   hepatoP↑, 4,   neuroP↑, 1,   radioP↑, 2,   toxicity↝, 1,   toxicity∅, 1,   TumVol↓, 2,  
Total Targets: 149

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 1,   GSH↑, 2,   GSTs↑, 1,   HO-1↑, 1,   lipid-P?, 1,   lipid-P↓, 2,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 5,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   iNOS↓, 2,   p‑JNK↓, 1,   MAPK↓, 2,   necrosis↓, 1,   p38↓, 1,   p‑p38↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

p‑ERK↓, 2,  

Migration ⓘ

5LO↓, 1,   TIMP1↓, 1,   α-SMA↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,  

Barriers & Transport ⓘ

BBB?, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IL1β↓, 1,   IL4↓, 1,   IL8↓, 1,   Inflam↓, 3,   NF-kB↓, 2,   TLR4↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,   BChE↓, 1,   tau↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,   NLRP3↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↝, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   GutMicro↑, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   hepatoP↑, 2,   memory↑, 1,   neuroP↑, 3,   Strength↑, 1,   toxicity↓, 1,   toxicity∅, 1,  
Total Targets: 51

Scientific Paper Hit Count for: ERK, ERK signaling
12 Silymarin (Milk Thistle) silibinin
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#:154  Target#:105  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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