Gli Cancer Research Results

Gli, GLI: Click to Expand ⟱
Source:
Type: protein/gene
The GLI gene family consists of three members: GLI1, GLI2, and GLI3. These genes encode transcription factors that play crucial roles in the Hedgehog signaling pathway, which is important for various developmental processes and cellular functions.
: In many cancers, aberrant activation of the Hedgehog signaling pathway leads to increased GLI expression. This can occur through mutations in Hedgehog pathway components or through the overexpression of Hedgehog ligands.

-GLI factors are implicated in maintaining cancer stem cell populations. These cells often drive tumor recurrence, metastasis, and resistance to therapy because they have self-renewal capabilities. The overactivation of GLI may, therefore, help sustain these subpopulations within tumors.

Elevated GLI expression levels can serve as a prognostic marker in certain cancers, indicating a more aggressive disease and poorer outcomes.
Scientific Papers found: Click to Expand⟱
2639- Api,    Plant flavone apigenin: An emerging anticancer agent
- Review, Var, NA
*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).

22- EGCG,    Inhibition of sonic hedgehog pathway and pluripotency maintaining factors regulate human pancreatic cancer stem cell characteristics
- in-vitro, PC, CD133+ - in-vitro, PC, CD44+ - in-vitro, PC, CD24+ - in-vitro, PC, ESA+
HH↓, EGCG also inhibited the components of Shh pathway (smoothened, patched, Gli1 and Gli2)
Smo↓,
PTCH1↓,
PTCH2↓,
Gli1↓,
GLI2↓,
Gli↓,
Bcl-2↓, inhibiting the expression of Bcl-2 and XIAP, and activating caspase-3
XIAP↓,
Shh↓,
survivin↓,
Casp3↑,
Casp7↑,
CSCs↓, EGCG inhibited the expression of pluripotency maintaining transcription factors (Nanog, c-Myc and Oct-4), and self-renewal capacity of pancreatic CSCs.
Nanog↓,
cMyc↓,
OCT4↓,
EMT↓, EGCG inhibited EMT by inhibiting the expression of Snail, Slug and ZEB1, and TCF/LEF transcriptional activity,
Snail↓,
Slug↓,
Zeb1↓,
TumCMig↓, significantly reduced CSC’s migration and invasion, suggesting the blockade of signaling involved in early metastasis.
TumCI↓,
eff↑, combination of quercetin with EGCG had synergistic inhibitory effects on self-renewal capacity of CSCs through attenuation of TCF/LEF and Gli activities

1733- SFN,    Sonic Hedgehog Signaling Inhibition Provides Opportunities for Targeted Therapy by Sulforaphane in Regulating Pancreatic Cancer Stem Cell Self-Renewal
- in-vitro, PC, PanCSC - in-vitro, Nor, HPNE - in-vitro, Nor, HNPSC
CSCs↓, In an in vitro model, human pancreatic CSCs derived spheres were significantly inhibited on treatment with SFN
Shh↓, SFN inhibited the components of Shh pathway and Gli transcriptional activity
Gli↓,
Nanog↓, suppressing the expression of pluripotency maintaining factors (Nanog and Oct-4) as well as PDGFRα and Cyclin D1
OCT4↓,
PDGFRA↓,
cycD1/CCND1↑,
Apoptosis↑, SFN induced apoptosis by inhibition of BCL-2 and activation of caspases
Casp↑,
Smo↓, SFN inhibited the expression of Smo, Gli1 and Gli2.
Gli1↓,
GLI2↓,
Bcl-2↓, SFN induced apoptosis in pancreatic CSCs by inhibiting Bcl-2 expression and through the activation of caspase 3/7
Casp3↑,
Casp7↑,

107- SS,    Saikosaponin B1 and Saikosaponin D inhibit tumor growth in medulloblastoma allograft mice via inhibiting the Hedgehog signaling pathway
- vitro+vivo, MB, LS174T
HH↓, SSB1 and SSD inhibit Hedgehog signaling pathway activity in vitro
Smo↓, SSB1 and SSD potentially inhibit the Hedgehog pathway by targeting SMO
Gli↓, luciferase
Gli1↓,
PTCH1↓,
TumCG↓, Inhibition of cell proliferation and tumor growth tumor growth inhibition ratios were approximately 50% and 70%,


Showing Research Papers: 1 to 4 of 4

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 4

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

NRF2↓, 1,   ROS↑, 1,   SOD↓, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 2,   NADPH↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↑, 1,   Bax:Bcl2↑, 1,   Bcl-2↓, 2,   Casp↑, 1,   Casp12↑, 1,   Casp3↑, 3,   Casp7↑, 2,   Casp9↑, 1,   CK2↓, 1,   Cyt‑c↑, 1,   p27↑, 1,   p38↑, 1,   survivin↓, 1,   Telomerase↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

DNA Damage & Repair ⓘ

cl‑PARP↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 1,   cycD1/CCND1↑, 1,   CycD3↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 3,   EMT↓, 1,   FOXO3↑, 1,   Gli↓, 4,   Gli1↓, 3,   HDAC↓, 1,   HDAC1↓, 1,   HDAC3↓, 1,   HH↓, 2,   IGF-1↓, 1,   Nanog↓, 2,   OCT4↓, 2,   PDGFRA↓, 1,   PI3K↓, 1,   PTCH1↓, 2,   PTCH2↓, 1,   Shh↓, 2,   Smo↓, 3,   STAT3↓, 2,   TumCG↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   FAK↓, 1,   GLI2↓, 2,   MMP2↓, 1,   MMP9↓, 1,   Slug↓, 1,   Snail↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   Twist↓, 1,   uPA↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   Hif1a↓, 1,   VEGF↓, 1,  

Barriers & Transport ⓘ

GLUT1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL6↓, 1,   IL8↓, 1,   NF-kB↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioEnh↑, 1,   ChemoSen↑, 1,   eff↑, 1,   eff↝, 1,  

Clinical Biomarkers ⓘ

HER2/EBBR2↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   chemoPv↑, 1,  
Total Targets: 80

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 2

Scientific Paper Hit Count for: Gli, GLI
1 Apigenin (mainly Parsley)
1 EGCG (Epigallocatechin Gallate)
1 Sulforaphane (mainly Broccoli)
1 Saikosaponin B1 and D
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#:%  Target#:434  State#:%  Dir#:1
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