condition found tbRes List
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 bioA (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 on acheive 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. Given low bioavailability seems unlikely one could acheieve levels in vivo to raise ROS(except 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↓, 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↓, OXPHOS↓, GRP78↑, 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


TumCG, Tumor cell growth: Click to Expand ⟱
Source:
Type:
Normal cells grow and divide in a regulated manner through the cell cycle, which consists of phases (G1, S, G2, and M).
Cancer cells often bypass these regulatory mechanisms, leading to uncontrolled proliferation. This can result from mutations in genes that control the cell cycle, such as oncogenes (which promote cell division) and tumor suppressor genes (which inhibit cell division).
Scientific Papers found: Click to Expand⟱
3578- CUR,  SIL,    Curcumin, but not its degradation products, in combination with silibinin is primarily responsible for the inhibition of colon cancer cell proliferation
- in-vitro, CRC, DLD1
eff↑, combination of curcumin and silymarin exhibited synergistic anticancer activity.
BioAv↓, Despite the low bioavailability of curcumin and the relatively low daily dietary intake (Shen et al. 2016, Teiten et al. 2010, Tsuda 2018), the beneficial effect of curcumin observed could be due to other phytochemicals present in the diet and act sy
TumCG↓, curcumin and silibinin in combination inhibit cell growth significantly

1001- SIL,    Silibinin down-regulates PD-L1 expression in nasopharyngeal carcinoma by interfering with tumor cell glycolytic metabolism
- in-vitro, NA, NA
TumCG↓,
Glycolysis↓, Silibinin potently inhibits tumor growth and promotes a shift from aerobic glycolysis toward oxidative phosphorylation.
OXPHOS↑,
LDHA↓,
lactateProd↓,
i-citrate↑,
Hif1a↓,
PD-L1↓, silibinin can alter PD-L1 expression by interfering with HIF-1α/LDH-A

1140- SIL,    Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth
- in-vitro, PC, AsPC-1 - in-vivo, PC, NA - in-vitro, PC, MIA PaCa-2 - in-vitro, PC, PANC1 - in-vitro, PC, Bxpc-3
TumCG↓,
Glycolysis↓,
cMyc↓,
STAT3↓,
TumCP↓,
Weight∅, prevents the loss of body weight and muscle.
Strength↑,
DNAdam↑,
Casp3↑,
Casp9↑,
GLUT1↓,
HK2↓,
LDHA↓,
GlucoseCon↓, silibinin inhibits glucose uptake and lactate release
lactateProd↓,
PPP↓, significant reduction in pentose phosphate pathway (PPP) metabolites, including 6-phosphogluconate (~50%), erythrose-4-phosphate (~40%), sedoheptulose-7-phosphate and sedoheptulose bis-phosphate (~ 70%)
Ki-67↓, reduced Ki67-positive cells
p‑STAT3↓,
cachexia↓,

2410- SIL,    Autophagy activated by silibinin contributes to glioma cell death via induction of oxidative stress-mediated BNIP3-dependent nuclear translocation of AIF
- in-vitro, GBM, U87MG - in-vitro, GBM, U251 - in-vivo, NA, NA
TumAuto↑, Mechanistically, silibinin activates autophagy through depleting ATP by suppressing glycolysis.
ATP↓,
Glycolysis↓, Silibinin suppressed glycolysis in glioma cells
H2O2↑, Then, autophagy improves intracellular H2O2 via promoting p53-mediated depletion of GSH and cysteine and downregulation of xCT
P53↑,
GSH↓,
xCT↓,
BNIP3↝, The increased H2O2 promotes silibinin-induced BNIP3 upregulation and translocation to mitochondria
MMP↑, silibinin-induced mitochondrial depolarization, accumulation of mitochondrial superoxide
mt-ROS↑,
mtDam↑, Autophagy contributed to silibinin-induced mitochondria damage
HK2↓, protein levels of HK II, PFKP, and PKM2 were all downregulated time-dependently by silibinin in U87, U251, SHG-44, and C6 glioma cells
PFKP↓,
PKM2↓, silibinin suppressed glycolysis via downregulation of HK II, PFKP, and PKM2.
TumCG↓, Silibinin inhibited glioma cell growth in vivo

3282- SIL,    Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions
- Review, NA, NA
hepatoP↑, This group of flavonoids has been extensively studied and they have been used as hepato-protective substances
AntiCan↑, however, silymarin compounds have clear anticancer effects
TumCMig↓, decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, i
Hif1a↓, In prostate cancer cells silibinin inhibited HIF-1α translation
selectivity↑, antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected
toxicity∅, long history of silymarin use in human diseases without toxicity after prolonged administration.
*antiOx↑, as an antioxidant, by scavenging prooxidant free radicals
*Inflam↓,
*NA↓, antiinflammatory effects similar to those of indomethacin,
TumCCA↑, MDA-MB 486 breast cancer cells, G1 arrest was found due to increased p21 and decreased CDKs activity
P21↑,
CDK4↓,
NF-kB↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
ERK↓, human prostate carcinoma cells, silymarin decreased ligand binding to Erb1 135 and NF-kB expression was strongly inhibited by silymarin in hepatoma cell
PSA↓, Treating prostate carcinoma cells with silymarin the levels of PSA were significantly decreased and cell growth was inhibited through decreased CDK activity and induction of Cip1/p21 and Kip1/p27. 1
TumCG↓,
p27↑,
COX2↓, such as anti-COX2 and anti-IL-1α activity, 140 antiangiogenic effects through inhibition of VEGF secretion, upregulation of Insulin like Growth Factor Binding Protein 3 (IGFBP3), 141 and inhibition of androgen receptors.
IL1↓,
VEGF↓,
IGFBP3↑,
AR↓,
STAT3↓, downregulation of the STAT3 pathway which was seen in many cell models.
Telomerase↓, silymarin has the ability to decrease telomerase activity in prostate cancer cells
Cyt‑c↑, mitochondrial cytochrome C release-caspase activation.
Casp↑,
eff↝, Malignant p53 negative cells show only minimal apoptosis when treated with silymarin. Therefore, one conclusion is that silymarin may be useful in tumors with conserved p53.
HDAC↓, inhibit histone deacetylase activity;
HATs↑, increase histone acetyltransferase activity
Zeb1↓, reduce expression of the transcription factor ZEB1
E-cadherin↑, increase expression of E-cadherin;
miR-203↑, increase expression of miR-203
NHE1↓, reduce activation of sodium hydrogen isoform 1 exchanger (NHE1)
MMP2↓, target β catenin and reduce the levels of MMP2 and MMP9
MMP9↓,
PGE2↓, reduce activation of prostaglandin E2
Vim↓, suppress vimentin expression
Wnt↓, inhibit Wnt signaling
angioG↓, Silymarin inhibits angiogenesis.
VEGF↓, VEGF downregulation
*TIMP1↓, Silymarin has the capacity to decrease TIMP1 expression166–168 in mice.
EMT↓, found that silibinin had no effect on EMT. However, the opposite was found in other malignant tissues160–162 where it showed inhibitory effects.
TGF-β↓, Silibinin reduces the expression of TGF β2 in different tumors such as triple negative breast, 174 prostate, and colorectal cancers.
CD44↓, Silibinin decreased CD44 expression and the activation of EGFR (epidermal growth factor receptor)
EGFR↓,
PDGF↓, silibinin had the ability to downregulate PDFG in fibroblasts, thus decreasing proliferation.
*IL8↓, Flavonoids, in general, reduce levels of IL-8. Curcumin, 200 apigenin, 201 and silybin showed the ability to decrease IL-8 levels
SREBP1↓, Silymarin inhibited STAT3 phosphorylation and decreased the expression of intranuclear sterol regulatory element binding protein 1 (SREBP1), decreasing lipid synthesis.
MMP↓, reduced membrane potential and ATP content
ATP↓,
uPA↓, silibinin decreased MMP2, MMP9, and urokinase plasminogen activator receptor level (uPAR) in neuroblastoma cells. uPAR is also a marker of cell invasion.
PD-L1↓, Silibinin inhibits PD-L1 by impeding STAT5 binding in NSCLC.
NOTCH↓, Silybin inhibited Notch signaling in hepatocellular carcinoma cells showing antitumoral effects
*SIRT1↑, Silymarin can also increase SIRT1 expression in other tissues, such as hippocampus, 221 articular chondrocytes, 222 and heart muscle
SIRT1↓, Silymarin seems to act differently in tumors: in lung cancer cells SIRT downregulated SIRT1 and exerted multiple antitumor effects such as reduced adhesion and migration and increased apoptosis.
CA↓, Silymarin has the ability to inhibit CA isoforms CA I and CA II.
Ca+2↑, ilymarin increases mitochondrial release of Ca++ and lowers mitochondrial membrane potential in cancer cell
chemoP↑, Silymarin: Decreasing Side Effects and Toxicity of Chemotherapeutic Drugs
cardioP↑, There is also evidence that it protects the heart from doxorubicin toxicity, however, it is less potent than quercetin in this effect.
Dose↝, oral administration of 240 mg of silybin to 6 healthy volunteers the following results were obtained 377 : maximum\,plasmaconcentration0.34±0.16⁢𝜇⁢g/m⁢L
Half-Life↝, and time to maximum plasma concentration 1.32 ± 0.45 h. Absorption half life 0.17 ± 0.09 h, elimination half life 6.32 ± 3.94 h
BioAv↓, silymarin is not soluble in water and oral administration shows poor absorption in the alimentary tract (approximately 1% in rats,
BioAv↓, Our conclusion is that, from a bioavailability standpoint, it is much easier to achieve migration inhibition, than proliferative reduction.
BioAv↓, Combination with succinate: is available on the market under the trade mark Legalon® (bis hemisuccinate silybin). Combination with phosphatidylcholine:
toxicity↝, 13 g daily per os divided into 3 doses was well tolerated. The most frequent adverse event was asymptomatic liver toxicity.
Half-Life↓, It may be necessary to administer 800 mg 4 times a day because the half-life is short.
ROS↓, its ability as an antioxidant reduces ROS production
FAK↓, Silibinin decreased human osteosarcoma cell invasion through Erk inhibition of a FAK/ERK/uPA/MMP2 pathway

3301- SIL,    Critical review of therapeutic potential of silymarin in cancer: A bioactive polyphenolic flavonoid
- Review, Var, NA
Inflam↓, graphical abstract
TumCCA↑,
Apoptosis↓,
TumMeta↓,
TumCG↓,
angioG↓,
chemoP↑, The chemo-protective effects of silymarin and silibinin propose that they could be applied to decrease the side effects and increase the anti-tumor effects of chemotherapy and radiotherapy in different types of cancers.
radioP↑,
p‑ERK↓, fig 2
p‑p38↓,
p‑JNK↓,
P53↑,
Bcl-2↓,
Bcl-xL↓,
TGF-β↓,
MMP2↓,
MMP9↓,
E-cadherin↑,
Wnt↓,
Vim↓,
VEGF↓,
IL6↓,
STAT3↓,
*ROS↓,
IL1β↓,
PGE2↓,
CDK1↓, Causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9,
CycB↓,
survivin↓,
Mcl-1↓,
Casp3↑,
Casp9↑,
cMyc↓, Silibinin treatment diminishes c-MYC
COX2↓, Silibinin considerably down-regulated the expression of COX-2, HIF-1α, VEGF, Ang-2, Ang-4, MMP-2, MMP-9, CCR-2 and CXCR-4
Hif1a↓,
CXCR4↓,
CSCs↓, HCT-116 cells, Induction of apoptosis, suppression of migration, elimination of CSCs. Attenuation of EMT via decreased expression of N- cadherin and vimentin and increased expression of (E-cadherin).
EMT↓,
N-cadherin↓,
PCNA↓, Decrease in PCNA and cyclin D1 level.
cycD1↓,
ROS↑, Hepatocellular carcinoma: Silymarin nanoemulsion reduced the cell viability and increased ROS intensity and chromatin condensation.
eff↑, Silymarin + Curcumin
eff↑, Silibinin + Metformin
eff↑, Silibinin + 1, 25-vitamin D3
HER2/EBBR2↓, Significant down regulation of HER2 by 150 and 250 µM of silybin after 24, 48 and 72 h.


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Results for Effect on Cancer/Diseased Cells:
angioG↓,2,   AntiCan↑,1,   Apoptosis↓,1,   AR↓,1,   ATP↓,2,   Bcl-2↓,1,   Bcl-xL↓,1,   BioAv↓,4,   BNIP3↝,1,   CA↓,1,   Ca+2↑,1,   cachexia↓,1,   cardioP↑,1,   Casp↑,1,   Casp3↑,2,   Casp9↑,2,   CD44↓,1,   CDK1↓,1,   CDK4↓,1,   chemoP↑,2,   i-citrate↑,1,   cMyc↓,2,   COX2↓,2,   CSCs↓,1,   CXCR4↓,1,   CycB↓,1,   cycD1↓,1,   Cyt‑c↑,1,   DNAdam↑,1,   Dose↝,1,   E-cadherin↑,2,   eff↑,4,   eff↝,1,   EGFR↓,1,   EMT↓,2,   ERK↓,1,   p‑ERK↓,1,   FAK↓,1,   GlucoseCon↓,1,   GLUT1↓,1,   Glycolysis↓,3,   GSH↓,1,   H2O2↑,1,   Half-Life↓,1,   Half-Life↝,1,   HATs↑,1,   HDAC↓,1,   hepatoP↑,1,   HER2/EBBR2↓,1,   Hif1a↓,3,   HK2↓,2,   IGFBP3↑,1,   IL1↓,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,1,   p‑JNK↓,1,   Ki-67↓,1,   lactateProd↓,2,   LDHA↓,2,   Mcl-1↓,1,   miR-203↑,1,   MMP↓,1,   MMP↑,1,   MMP2↓,2,   MMP9↓,2,   mtDam↑,1,   N-cadherin↓,1,   NF-kB↓,1,   NHE1↓,1,   NOTCH↓,1,   OXPHOS↑,1,   P21↑,1,   p27↑,1,   p‑p38↓,1,   P53↑,2,   PCNA↓,1,   PD-L1↓,2,   PDGF↓,1,   PFKP↓,1,   PGE2↓,2,   PKM2↓,1,   PPP↓,1,   PSA↓,1,   radioP↑,1,   ROS↓,1,   ROS↑,1,   mt-ROS↑,1,   selectivity↑,1,   SIRT1↓,1,   SREBP1↓,1,   STAT3↓,3,   p‑STAT3↓,1,   Strength↑,1,   survivin↓,1,   Telomerase↓,1,   TGF-β↓,2,   toxicity↝,1,   toxicity∅,1,   TumAuto↑,1,   TumCCA↑,2,   TumCG↓,6,   TumCMig↓,1,   TumCP↓,1,   TumMeta↓,1,   uPA↓,1,   VEGF↓,3,   Vim↓,2,   Weight∅,1,   Wnt↓,2,   xCT↓,1,   Zeb1↓,1,  
Total Targets: 112

Results for Effect on Normal Cells:
antiOx↑,1,   IL8↓,1,   Inflam↓,1,   NA↓,1,   ROS↓,1,   SIRT1↑,1,   TIMP1↓,1,  
Total Targets: 7

Scientific Paper Hit Count for: TumCG, Tumor cell growth
6 Silymarin (Milk Thistle) silibinin
1 Curcumin
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:154  Target#:323  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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