Gli1 Cancer Research Results

Gli1, glioma-associated oncogene homolog 1: Click to Expand ⟱

Source:

Type: HH

Gli family zinc-finger transcription factors; GLI1‐dependent target genes (CyclinD1, Bcl‐2, Foxm1)

Glioma-associated oncogene homolog 1 (GLI1) is a transcription factor that plays a significant role in the Hedgehog signaling pathway, which is crucial for cell growth, differentiation, and tissue patterning during embryonic development.
GLI1 can promote tumor growth and survival by regulating the expression of genes involved in cell proliferation, apoptosis, and angiogenesis. Its overexpression has been associated with aggressive tumor behavior and poor prognosis in several cancer types.
ts overexpression is often associated with aggressive tumor behavior, poor prognosis, and resistance to therapy

Scientific Papers found: Click to Expand⟱

Aco,

Recent development on hyperthermia: An effective cotreatment improving radiotherapy outcome

in-vitro,

PC,

PANC1

in-vitro,

Pca,

DU145

HH↓, As an adjunct to radiotherapy and chemotherapy, hyperthermia enhances the therapeutic efficacy against both primary and recurrent tumors.
PTCH1↓, The present review explores the mechanisms underlying the synergy between radiotherapy and hyperthermia, while reviewing the outcomes of relevant clinical trials.
Bcl-2↓, Key mechanisms of action include inhibition of DNA repair, reduction of hypoxic tumor cell populations, enhancement of drug uptake and improved perfusion and oxygenation.
Gli1↓,

1353-

And,

Andrographolide Induces Apoptosis and Cell Cycle Arrest through Inhibition of Aberrant Hedgehog Signaling Pathway in Colon Cancer Cells

in-vitro,

Colon,

HCT116

ChemoSen↑, combination with 5FU, andrographolide exhibited synergistic effect
TumCCA↑, G2/M phase arrest
CDK1↓,
CycB/CCNB1↓,
HH↓, repressed the colon cancer cell growth via inhibiting Hh signaling pathway
Smo↓,
Gli1↓,

Api,

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

in-vitro,

Pca,

HH↓,
Gli1↓,

275-

Api,

Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3‑derived sphere-forming cells

in-vitro,

Ovarian,

SKOV3

HH↓,
CK2↓, CK2α
Gli1↓,

Ba,

Api,

QC,

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

in-vitro,

Pca,

PC3

HH↓, Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer
Gli1↓, three compounds, apigenin, baicalein, and quercetin, decreased Gli1 mRNA concentration but not Gli reporter activity

2617-

Ba,

Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review

Review,

Var,

Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1 / PDPK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2/KDR/Flk1↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

BetA,

Hedgehog/GLI-mediated transcriptional inhibitors from Zizyphus cambodiana

in-vitro,

PC,

HaCaT

in-vitro,

Pca,

PANC1

HH↓,
Gli1↓, The expressions of GLI-related proteins PTCH and BCL2 were clearly inhibited by 1 or 2.
PTCH1↓,
Bcl-2↓,

2736-

BetA,

Chemo,

Multifunctional Roles of Betulinic Acid in Cancer Chemoprevention: Spotlight on JAK/STAT, VEGF, EGF/EGFR, TRAIL/TRAIL-R, AKT/mTOR and Non-Coding RNAs in the Inhibition of Carcinogenesis and Metastasis

Review,

Var,

chemoPv↑, reviews about cancer chemopreventive role of betulinic acid against wide variety of cancers [18,19,20,21].
p‑STAT3↓, betulinic acid reduced the levels of p-STAT3 in tumor tissues derived from KB cells
JAK1↓, Betulinic acid exerted inhibitory effects on the constitutive phosphorylation of JAK1 and JAK2
JAK2↓,
VEGF↓, betulinic acid mediated inhibition of VEGF
EGFR↓, evaluation of betulinic acid as a next-generation EGFR inhibitor
Cyt‑c↑, release of SMAC/DIABLO and cytochrome c from mitochondria in SHEP neuroblastoma cells
Diablo↑,
AMPK↑, Betulinic acid induced activation of AMPK and consequently reduced the activation of mTOR.
mTOR↓,
Sp1/3/4↓, Betulinic acid significantly reduced the quantities of Sp1, Sp3 and Sp4 in the tissues of the tumors derived from RKO cells
DNAdam↑, Betulinic acid efficiently triggered DNA damage (γH2AX) and apoptosis (caspase-3 and p53 phosphorylation) in temozolomide-sensitive and temozolomide-resistant glioblastoma cells.
Gli1↓, Betulinic acid effectively reduced GLI1, GLI2 and PTCH1 in RMS-13 cells.
GLI2↓,
PTCH1↓,
MMP2↓, betulinic acid exerted inhibitory effects on MMP-2 and MMP-9 in HepG2 cells.
MMP9↓,
miR-21↓, Collectively, p53 increased miR-21 levels and inhibited SOD2 levels, leading to significant increase in the accumulation of ROS levels and apoptotic cell death.
SOD2↓,
ROS↑,
Apoptosis↑,

5893-

CAR,

TV,

Thymol and Carvacrol: Molecular Mechanisms, Therapeutic Potential, and Synergy With Conventional Therapies in Cancer Management

Review,

Var,

*Inflam↓, Monoterpenes like thymol and carvacrol are recognized for their anti‐inflammatory and anticancer properties,
AntiCan↑,
PI3K↓, Thymol derivatives, such as 1,2,3‐triazoles and carvacrol, effectively target breast cancer (BC) through PI3K/AKT/mTOR and NOTCH pathways and inhibit PIK3CA expression.
Akt↓,
mTOR↓,
NOTCH↓,
PIK3CA↓,
EGFR↓, thymol exhibits anti‐EGFR activity, while carvacrol modulates the HIF‐1α/VEGF pathway, making them potential candidates for colorectal cancer (CRC) management.
Hif1a↓,
VEGF↓,
ChemoSen↑, Their synergistic potential with chemotherapy, radiotherapy, and other bioactive compounds strengthens their therapeutic promise.
RadioS↑,
eff↝, challenges such as stability, bioavailability, and the need for clinical trials hinder their clinical application.
*cardioP↑, cardioprotective (Joshi et al. 2023), neuroprotective (Forqani et al. 2023) and hepato‐nephroprotective
*neuroP↑,
*hepatoP↑,
Apoptosis↑, Induction of Apoptosis
MMP↓, The apoptosis was due to ROS production, variations in the mitochondrial membrane, caspase‐3 activation, and DNA damage
Casp3↑,
ROS↑,
DNAdam↑,
eff↑, Thymol derivative, known as compound 10 (IC50 6.17 μM) exhibited 3.2‐fold more inhibition than 5‐fluorouracil (IC50 20.09 μM) against MCF‐7
BAX↑, Carvacrol (25, 50, 75, and 90 μM) enhanced the expression of Bax, Bad, Fas‐L, and cytochrome c, activated caspase‐9/3 and caspase‐8, induced cell cycle at G0/G1
BAD↑,
FasL↑,
Cyt‑c↑,
Casp9↑,
Casp8↑,
TumCCA↑,
P21↑, improved the expression of proteins (p21, cyclin D1, CDK4), and downregulated the SMO and GLI1 proteins expression in CC
Smo↓,
Gli1↓,
JNK↑, Moreover, thymol activated JNK and p38 MAPK while impeding the ERK pathway
ERK↓,
MAPK↓, Besides thymol, carvacrol has also been reported to inhibit MAPK or ERK pathways in previous studies.
TRPM7↓, inhibited TRPM7 expression in liver fibrotic C57BL/6J mice
Wnt/(β-catenin)↓, hymol inhibited HCT116 and LoVo cell line invasion via downregulating the Wnt/β‐catenin pathway and reducing c‐Myc and Cyclin D1 expression
BioAv↝, thymol and carvacrol are volatile, and their stability is influenced by these factors (temperature, light, oxygen, and pH)
BioAv↑, Ultrasonication is an effective technique to enhance the stability of thymol and other bioactive compounds. 400 watts of power elevated the performance of NC‐CH formulations, and NC‐CH‐400 displayed increased solubility.

17-

CBC/D,

CBC-1 as a Cynanbungeigenin C derivative inhibits the growth of colorectal cancer through targeting Hedgehog pathway component GLI 1

in-vivo,

CRC,

HH↓, CBC-1 inhibited the proliferation of CRC cells through regulation of mRNA and proteins of the HH pathway
Gli1↓, indicated that CBC-1 regulated this signalling pathway by targeting glioma-associated oncogene (GLI 1
BioAv↓, Cynanbungeigenin C (CBC) is a new type of C21 steroid that has been previously reported for the treatment of medulloblastoma. However, its further investigation was limited by its poor water solubility
TumCP↓, It was found that CBC-1 presented the best inhibitory effect on three types of CRC cell lines, and this effect was superior to that of CBC.

18-

CBC/D,

Cynanbungeigenin C and D, a pair of novel epimers from Cynanchum bungei, suppress hedgehog pathway-dependent medulloblastoma by blocking signaling at the level of Gli

vitro+vivo,

MB,

HH↓, Mechanistically, CBC and CBD block Hh pathway signaling not through targeting Smo and Sufu, but at the level of Gli
Gli1↓,

6253-

CBC/D,

The SHH/GLI signaling pathway: a therapeutic target for medulloblastoma

Review,

MB,

Gli1↓, Cynanbungeigenin C (CBC) and D (CBD) have been isolated from Cynanchum bungei Decne plant and have emerged as GLI1 inhibitors although with an unclear mechanism.
Dose↝, Both compounds are able to repress Gli1-luciferase reporter activity (IC50 values of 2.9 and 3.7 μM, respectively), and to inhibit HH signaling in cells expressing D473H and W535L drug-resistant SMO mutants
HH↓,
BBB↑, Of note, pharmacokinetic studies demonstrated the capability of these compounds to cross the BBB

411-

CUR,

Curcumin inhibits the invasion and metastasis of triple negative breast cancer via Hedgehog/Gli1 signaling pathway

in-vitro,

BC,

MDA-MB-231

HH↓,
EMT↓,
Gli1↓,

455-

CUR,

Curcumin Affects Gastric Cancer Cell Migration, Invasion and Cytoskeletal Remodeling Through Gli1-β-Catenin

in-vitro,

GC,

SGC-7901

10, 20, 40 and 80 µM, 48 h

Shh↓,
Gli1↓,
FOXM1↓,
β-catenin/ZEB1↓,
TumCMig↓, induced S phase cell cycle arrest
Apoptosis↑,
TumCCA↑,
Wnt↓,
EMT↓,
E-cadherin↑,
Vim↓,

12-

CUR,

Curcumin inhibits the Sonic Hedgehog signaling pathway and triggers apoptosis in medulloblastoma cells

in-vitro,

MB,

DAOY

 20 uM

HH↓, Curcumin inhibits the Sonic Hedgehog signaling pathway
Shh↓, curcumin inhibited the Shh-Gli1 signaling pathway by downregulating the Shh protein
Gli1↓,
PTCH1↓,
cMyc↓,
n-MYC↓,
cycD1/CCND1↓,
Bcl-2↓,
NF-kB↓,
Akt↓,
β-catenin/ZEB1↓, curcumin reduced the levels of beta-catenin
survivin↓,
Apoptosis↑, Consequently, apoptosis was triggered by curcumin through the mitochondrial pathway via downregulation of Bcl-2, a downstream anti-apoptotic effector of the Shh signaling.
ChemoSen↑, curcumin enhances the killing efficiency of nontoxic doses of cisplatin and gamma-rays.
RadioS↑,
eff↑, we present clear evidence that piperine, an enhancer of curcumin bioavailability in humans

11-

CUR,

Curcumin inhibits hypoxia-induced epithelial‑mesenchymal transition in pancreatic cancer cells via suppression of the hedgehog signaling pathway

in-vitro,

PC,

PANC1

HH↓, suppression of the hedgehog signaling pathway
Shh↓, Curcumin significantly decreased hypoxia-induced expression levels of SHH, SMO and GLI1.
Smo↓,
Gli1↓,
N-cadherin↓,
E-cadherin↑,
Vim↓,
TumCP↓, inhibit the hypoxia-induced cell proliferation, migration and invasion in pancreatic cancer,
TumCMig↓,
TumCI↓,
EMT↓, mediate the expression of EMT-related factors.
chemoPv↑, Curcumin might be a potential candidate for chemoprevention of this severe disease.

CUR,

Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH/GLI1 Signaling Pathway in Vitro and Vivo

vitro+vivo,

MG,

U87MG

 15uM

vitro+vivo,

MG,

T98G

 31uM
31 uM

HH↓, Both mRNA and protein levels of SHH/GLI1 signaling (Shh, Smo, GLI1) were downregulated in a dose‐ and time‐dependent manner
Shh↓, inhibition of SHH/GLI1 signaling by curcumin may act as a novel mechanism of the apoptosis.
Gli1↓,
cycD1/CCND1↓,
Bcl-2↓,
FOXM1↓,
Bax:Bcl2↑, The Bax/Bcl‐2 ratio (Figure 6D) also gradually increased.
TumCP↓, Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2.
TumCMig↓,
Apoptosis↑,
TumVol↑, Intraperitoneal injection of curcumin in vivo reduced tumor volume,
TumCCA↑, Curcumin Inhibited Proliferation of Human Glioma Cells and induced G2/M Arrest
Casp3↑, level of caspase‐3 increases significantly after curcumin treatment.
OS↑, Curcumin Inhibited GBM Growth in Vivo through SHH/GLI1 Signaling and Prolonged the Survival Period

16-

Cyc,

RES,

Resveratrol inhibits the hedgehog signaling pathway and epithelial-mesenchymal transition and suppresses gastric cancer invasion and metastasis

in-vitro,

GC,

SGC-7901

HH↓, decrease in Gli-1, Snail and N-cadherin expression, and an increase in E-cadherin expression in the resveratrol and cyclopamine group compared
Gli1↓,
EMT↓, suggesting that resveratrol inhibited the Hh pathway and EMT, as did cyclopamine.
N-cadherin↓,
E-cadherin↑,
Snail↓,
TumCI↓, suppress invasion and metastasis in gastric cancer in vitro.
TumMeta↓, Resveratrol and cyclopamine inhibits the metastasis and invasion of SGC-7901 cells

19-

Deg,

Deguelin inhibits proliferation and migration of human pancreatic cancer cells in vitro targeting hedgehog pathway

in-vitro,

PC,

Bxpc-3

in-vitro,

PC,

PANC1

 0-20uM-1wk

HH↓, The activation of the hedgehog (Hh) signaling pathway, as well as matrix metalloproteinases (MMP)-2 and MMP-9, was suppressed by deguelin.
Gli1↓,
PTCH1↓,
Sufu↓,
MMP2↓, Deguelin downregulates MMP-2 and MMP-9 in Bxpc-3 and Panc-1 cells
MMP9↓,
PI3K/Akt↓,
HIF-1↓,
VEGF↓,
IKKα↓,
NF-kB↓,
EMT↓,
AMPK↑,
mTOR↓,
survivin↓,
TumCG↓, Deguelin treatment was observed to inhibit growth and induce apoptosis in two PC cell lines (Bxpc-3 and Panc-1)
Apoptosis↑,
TumCMig↓, Deguelin inhibits migration and invasion of PC cells
TumCI↓,

27-

EA,

Ellagic acid inhibits human pancreatic cancer growth in Balb c nude mice

in-vivo,

PC,

PANC1

 PANC-1 cells were injected subcutaneously into Balb c nude mice, and tumor-bearing mice were treated with EA

HH↓,
Gli1↓, EA caused a significant inhibition in phospho-Akt, Gli1, Gli2, Notch1, Notch3, and Hey1.
GLI2↓,
CDK1/2/5/9↓,
p‑Akt↓,
NOTCH1↓,
Shh↓,
Snail↓,
E-cadherin↑,
NOTCH3↓,
HEY1↓,
TumCG↓, EA resulted in significant inhibition in tumor growth which was associated with suppression of cell proliferation and caspase-3 activation, and induction of PARP cleavage.
TumCP↓,
Casp3↑,
cl‑PARP↑,
Bcl-2↓, EA inhibited the expression of Bcl-2, cyclin D1, CDK2, and CDK6, and induced the expression of Bax in tumor tissues compared to untreated control group
cycD1/CCND1↓,
CDK2↓,
CDK6↓,
BAX↑,
COX2/PTGS2↓, EA inhibited the markers of angiogenesis (COX-2, HIF1α, VEGF, VEGFR, IL-6 and IL-8), and metastasis (MMP-2 and MMP-9) in tumor tissues.
Hif1a↓,
VEGF↓,
VEGFR2/KDR/Flk1↓,
IL6↓,
IL8↓,
MMP2↓,
MMP9↓,
NA↓, EA could effectively inhibit human pancreatic cancer growth by suppressing Akt, Shh and Notch pathways

20-

EGCG,

Potential Therapeutic Targets of Epigallocatechin Gallate (EGCG), the Most Abundant Catechin in Green Tea, and Its Role in the Therapy of Various Types of Cancer

in-vivo,

Liver,

in-vivo,

Tong,

HH↓,
Gli1↓,
Smo↓,
TNF-α↓,
COX2/PTGS2↓, EGCG inhibits cyclooxygenase-2 without affecting COX-1 expression at both the mRNA and protein levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3
*antiOx↑, EGCG is a well-known antioxidant and it scavenges most free radicals, such as ROS and RNS
Hif1a↓,
NF-kB↓,
VEGF↓,
STAT3↓,
Bcl-2↓,
P53↑, EGCG activates p53 in human prostate cancer cells
Akt↓,
p‑Akt↓,
p‑mTOR↓,
EGFR↓,
AP-1↓,
BAX↑,
ROS↑, apoptosis was convoyed by ROS production and caspase-3 cleavage
Casp3↑,
Apoptosis↑,
NRF2↑, pancreatic cancer cells via inducing cellular reactive oxygen species (ROS) accumulation and activating Nrf2 signaling
*H2O2↓, EGCG plays a role in the inhibition of H2O2 and NO production in human skin [10].
*NO↓, EGCG plays a role in the inhibition of H2O2 and NO production in human skin [10].
*SOD↑, fig 2
*Catalase↑, fig 2
*GPx↑, fig 2
*ROS↓, fig 2

21-

EGCG,

Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

in-vivo,

Liver,

HH↓, The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction
PTCH1↓,
Smo↓,
Gli1↓,
CD44↓, Both EGCG and TF significantly reduced (P b 0.05) CD44 positive cells in all the treated groups
β-catenin/ZEB1↓, GCG and TF could reduce β-catenin expression and its nu- clear activation in different cancers (

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+

 20-60 uM

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

23-

EGCG,

(-)-Epigallocatechin-3-gallate induces apoptosis and suppresses proliferation by inhibiting the human Indian Hedgehog pathway in human chondrosarcoma cells

in-vitro,

Chon,

SW1353

in-vitro,

Chon,

CRL-7891

HH↓, EGCG inhibited the human Indian Hedgehog pathway, down-regulated PTCH and Gli-1 levels,
Gli1↓,
PTCH1↓,
Bcl-2↓, Bcl-2 were significantly decreased and the levels of Bax were significantly increased.
BAX↑,
TumCG↓, EGCG is effective for growth inhibition of a chondrosarcoma cell lines in vitro, and suggest that EGCG may be a new therapeutic option for patients with chondrosarcoma.

651-

EGCG,

Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications

ROS↑, mounting evidence that EGCG can stimulate ROS production, which in turn leads to the phosphorylation and activation of AMPK
p‑AMPK↑,
mTOR↓,
FAK↓,
Smo↓,
Gli1↓,
HH↓,
TumCMig↓,
TumCI↓,
NOTCH↓,
JAK↓,
STAT↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
Casp9↑,

816-

GAR,

Garcinol downregulates Notch1 signaling via modulating miR-200c and suppresses oncogenic properties of PANC-1 cancer stem-like cells

in-vitro,

PC,

PANC1

significantly suppressed the stem-like properties

Mcl-1↓,
EZH2↓,
ABCG2↓,
Gli1↓,
NOTCH1↓,
miR-200c↑, miR-200c increased by garcinol treatment was found to target and downregulate Notch1.

28-

GEN,

Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway

in-vivo,

BC,

MCF7

 15-30 uM 20-50mg/kg(2wks)

HH↓, own-regulating Hedgehog-Gli1 signaling pathway.
Smo↓,
Gli1↓,
TumCG↓, Genistein inhibited the MCF-7 breast cancer cells’ growth and proliferation and promoted apoptosis.
TumCP↓,
Apoptosis↑,
CSCs↓, genistein inhibits BCSCs by down-regulating Hedgehog-Gli1 signaling pathway.

29-

GEN,

Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway

in-vivo,

Pca,

22Rv1

in-vivo,

Pca,

DU145

HH↓, Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog-Gli1 pathway
Gli1↓, but also inhibited Hedgehog-Gli1 pathway
CSCs↓, genistein treatment not only led to the down-regulation of PCa CSC markers CD44 in vitro and in vivo
TumCI↓, genistein can inhibit PCa cell invasion by reversing epithelial to mesenchymal transition,
EMT↓,
TumCG↓, genistein treatment inhibited tumor growth of PCa TCs
CD44↓, CD44 was significantly down-regulated after the genistein treatment

166-

GEN,

EGCG,

RES,

CUR,

Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer

in-vivo,

Pca,

HH↓, The four compounds, which inhibited Hedgehog signaling in both cell assays (genistein, curcumin, EGCG, and resveratrol), are potentially cheaper and safer alternatives to cyclopamine
Gli1↓, Three compounds, apigenin, baicalein, and quercetin, decreased Gli1 mRNA concentration but not Gli reporter activity.

31-

GlaB,

Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors

in-vitro,

BCC,

HH↓, robust inhibitory effect on Gli1 activity, Glabrescione B inhibited the growth of Hedgehog-dependent tumor cells in vitro and in vivo
Gli1↓, GlaB inhibits Hh signaling by impairing Gli1 function
PTCH1↓,
CSCs↓, as well as the self-renewal ability and clonogenicity of tumor-derived stem cells.

32-

GlaB,

Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors

in-vivo,

MB,

HH↓, GlaB inhibits Hh signaling by imparing Gli1/DNA binding and transcriptional activity
Gli1↓, impairing Gli1 activity by interfering with its interaction with DNA
PTCH1↓,
TumCG↓, Glabrescione B inhibited the growth of Hedgehog-dependent tumor cells in vitro and in vivo
CSCs↓, s well as the self-renewal ability and clonogenicity of tumor-derived stem cells.

7297-

GlaB,

H-NMR metabolomics reveals the Glabrescione B exacerbation of glycolytic metabolism beside the cell growth inhibitory effect in glioma

vitro+vivo,

GBM,

TumCG↓, We found that GlaB affected the growth of murine glioma cells both in vitro and in vivo animal model.
Glycolysis↑, we found that GlaB stimulated the glycolytic metabolism in glioma, increasing lactate production.
lactateProd↑,
Warburg↑, Our results indicate that GlaB inhibits glioma cell growth and exacerbates Warburg effect, increasing lactate production.
eff↑, In addition, the simultaneous blockade of Gli1 and lactate efflux amplifies the anti-tumor effect in vivo, providing new potential therapeutic strategy for this brain tumor.
Gli1↓, GL261 cells overexpress Gli1 and its inhibition with GlaB induces cell apoptosis

7298-

GlaB,

Glycolytic Metabolic Remodeling by the Truncate of Glioma-Associated Oncogene Homolog 1 in Triple-Negative Breast Cancer Cells

in-vitro,

BC,

Gli1↓, However, Glabrescione B (GlaB, a GLI1 inhibitor) increases glucose uptake and lactate excretion, exacerbating the Warburg effect 35.
GlucoseCon↑,
lactateProd↝,
Warburg↑,

7299-

GlaB,

Functional and therapeutic effects of Glabrescione B delivery by liposomes on Hedgehog-dependent tumors

Gli1↓, Glabrescione B (GlaB), is a small molecule that directly inhibits Gli1/DNA interaction, which showed promising pre-clinical results.
BioAv↓, However, poor solubility limits its clinical translation.
BioAv↑, Lipo/GlaB inhibits Gli1 transcriptional activity more potently than free GlaB and significantly reduces the expression of HH target genes.
HH↓,
BioAv↓, we took advantage of innovative nanopharmaceuticals and we developed a micellar formulation using the biocompatible compound methoxy-poly (ethylene glycol)-cholane (mPEG-Cholane), which increases the GlaB solubility by a 100-fold.

7300-

GlaB,

ATO,

Targeting GLI1 and GLI2 with small molecule inhibitors to suppress GLI-dependent transcription and tumor growth

in-vitro,

Var,

Gli↓, To date, GANT61, arsenic trioxide (ATO) and Glabrescione B (GlaB) are the only direct GLI antagonists identified.
HH↓, GANT61 and GlaB have been reported to directly bind GLI1 and inhibit the canonical and noncanonical HH pathway
Gli1↓, More recently, the natural isoflavone GlaB was reported as a GLI1 inhibitor that interferes with the GLI1/DNA binding
BioAv↓, Nevertheless, GlaB is characterized by poor aqueous solubility

7301-

GlaB,

Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors

Gli1↓, Remarkably, as a consequence of its robust inhibitory effect on Gli1 activity, Glabrescione B inhibited the growth of Hedgehog-dependent tumor cells in vitro and in vivo
HH↓,

7302-

GlaB,

Glabrescione B delivery by self-assembling micelles efficiently inhibits tumor growth in preclinical models of Hedgehog-dependent medulloblastoma

vitro+vivo,

MB,

BioAv↑, mPEG5kDa-cholane efficiently enhances the solubility of GlaB, a selective GLI1 inhibitor.
Gli1↓, Glabrescione B (GlaB), a selective GLI1 inhibitor, were investigated in preclinical models of Hh-dependent MB.
TumCG↓, We showed that GlaB reduces tumor growth both in vitro and in vivo in MB and BCC models depending on specific Hh-activating mutation
Dose↝, CD1 WT mice (Charles River Laboratories, Lecco, Italy) treated with mPEG5kDa-cholane/GlaB (9 mg/kg) by i.v. injection.
BBB↑, GlaB loaded in mPEG5kDa-cholane micelles crosses the BBB and inhibits tumor growth in a Hh-dependent MB orthotopic model
HH↓,

843-

Gra,

Graviola (Annona muricata) Exerts Anti-Proliferative, Anti-Clonogenic and Pro-Apoptotic Effects in Human Non-Melanoma Skin Cancer UW-BCC1 and A431 Cells In Vitro: Involvement of Hedgehog Signaling

in-vitro,

NMSC,

A431

3.5 µg/mL

DCM fraction proved to be by far the most potent in inhibiting the proliferation

in-vitro,

NMSC,

UW-BCC1

4.0 µg/mL

in-vitro,

Nor,

NHEKn

38.8 µg/mL

10-fold higher than in noncancerous NHEKn cells

TumCG↓,
TumCCA↑, induce G0/G1 cell cycle arrest
Cyc↓,
Apoptosis↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑PARP↑,
HH↓,
Smo↓,
Gli1↓,
GLI2↓,
Shh↓,
Sufu↑,
BAX↑,
Bcl-2↓,
*toxicity↓, normal cells 10-fold higher IC50

30-

GSL,

A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli-mediated transcription in pancreatic cancer cells

in-vitro,

PC,

PANC1

 (IC 50) values of 6,.9 uM

in-vitro,

PC,

AsPC-1

 5.1 uM

HH↓, suppresses Hedgehog/Gli-mediated transcription in pancreatic cancer cells
Gli1↓,
Shh↓,
cycD1/CCND1↓, which resulted in reduced cancer cell proliferation and downregulated expression of the Gli-target genes, Gli1 and cyclin D1
TumCP↓,

108-

GSL,

A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli-mediated transcription in pancreatic cancer cells

in-vitro,

PC,

PANC1

  6.9 uM

in-vitro,

PC,

AsPC-1

  5.1 uM

in-vitro,

PC,

C3H10T1/2

  35.7 uM

HH↓, GSL suppressed Gli-mediated transcriptional activity in human pancreatic cancer PANC-1 and AsPC-1 cells, which resulted in reduced cancer cell proliferation and downregulated expression of the Gli-target genes, Gli1 and cyclin D1.
Gli1↓,
cycD1/CCND1↓,
TumCP↓, GSL dose-dependently suppressed proliferation of the pancreatic cancer cells, with 50% inhibitory concentration (IC50) values of 6.9 and 5.1 µM in PANC-1 and AsPC-1

7468-

HNK,

Honokiol and Its Emerging Role in Breast Cancer Therapy

Review,

BC,

*ROS↓, HNK inhibits essential oncogenic pathways and reduces oxidative stress, inflammation, metabolic reprogramming, and cancer stemness.
*Inflam↓,
CSCs↓,
ChemoSen↑, HNK demonstrates synergistic activity with chemotherapy, endocrine therapy, targeted therapy, and immune checkpoint inhibitors, increasing sensitivity to treatment across models of ER+, PR+, and HER2+ BrCas, as well as triple-negative breast cancers
BioAv↑, Nanotechnological delivery systems enhance the solubility, bioavailability, and intratumoral accumulation of HNK, increasing its translational capacity.
ROS↑, HNK increases intracellular reactive oxygen species (ROS) levels in cancer cells, coinciding with a time-dependent loss of mitochondrial membrane potential (ΔΨm), indicating that ROS production is closely linked to mitochondrial damage
MMP↓,
mtDam↑,
TumCCA↑, HNK causes G0/G1 cell cycle arrest by downregulating cyclin D1 and CDK4, as well as promoting intrinsic apoptosis-like pathways marked by increases in caspase-3 and caspase-9 activities
cycD1/CCND1↓,
CDK4↓,
Casp3↑,
Casp9↑,
Bcl-2↓, reducing the anti-apoptotic Bcl-2 and Bcl-xL, and increasing the pro-apoptotic Bax
Bcl-xL↓,
BAX↑,
p‑STAT3↓, HNK suppresses the phosphorylation of STAT3 in MDA-MB-231
AMPK↑, HNK was found to activate the LKB1–AMPK axis and induce miR-34a expression in MCF7, SKBR3, and SUM149 cells, thereby inhibiting EMT, stemness, and oncogenic leptin signaling in an LKB1-dependent manner
miR-34a↑,
EMT↓,
HH↓, HNK can induce apoptosis by suppressing essential components of the Hh pathway, including SHH [28], Gli1, and Ptch1 [26], as well as downregulating NF-κB
Shh↓,
Gli1↓,
PTCH1↓,
NF-kB↓,
TNF-α↓, reduces the production of inflammatory cytokines, including TNF-α and IL-6
IL6↓,
Glycolysis↓, HNK suppresses HIF-1α-controlled glycolysis by downregulating glycolytic metabolic enzymes, disrupting glucose uptake, and inhibiting tumor growth.
GlucoseCon↓,
BioAv↓, This limitation is primarily attributed to pharmacokinetic challenges, including poor aqueous solubility, low oral bioavailability, rapid metabolism, and the lack of standardized dosing regimens,
BioAv↓, Preclinical studies demonstrate that following oral administration at 40 mg/kg, HNK is rapidly absorbed (Tmax ≈ 20 min) but exhibits low systemic exposure [75], due to extensive first-pass metabolism and high hepatic extraction
Half-Life↝, While the plasma elimination half-life is moderately prolonged (t½ ≈ 290 min),

8011-

itraC,

Anti-proliferation of breast cancer cells with itraconazole: Hedgehog pathway inhibition induces apoptosis and autophagic cell death

vitro+vivo,

BC,

MCF7

human xenograft nude mouse model

vitro+vivo,

BC,

SkBr3

MMP↓, itraconazole was cytotoxic to MCF-7 and SKBR-3 breast cancer cell lines via apoptosis by altering mitochondria membrane potential, reducing BCL-2 expression and elevating caspase-3 activity
Bcl-2↓,
Casp3↑,
TumAuto↑, Itraconazole also induced autophagic cell death via LC3-II expression upregulation, P62/SQSTM1 degradation, autophagosome formation and increases in autophagic puncta
LC3II↑,
p62↓,
HH↓, Itraconazole treatment inhibited hedgehog pathway key molecular expression, such as SHH and Gli1, resulting in promotion of apoptosis and autophagy.
Shh↓,
Gli1↓,
Apoptosis↑,
TumVol↓, A human xenograft nude mouse model corroborated the anti-breast cancer activity as evidenced by reduced tumor size, and increased tumor tissue apoptosis and autophagy.
eff↑, itraconazole has a potent anti-breast cancer activity that may be improved when combined with hedgehog pathway inhibitors.
TumCCA↑, G0/G1 cell cycle arrest

8010-

itraC,

Itraconazole induces apoptosis and cell cycle arrest via inhibiting Hedgehog signaling in gastric cancer cells

vitro+vivo,

GC,

MKN45

xenograft model

TumCP↓, Itraconazole could remarkably inhibit the proliferation of gastric cancer cells
ChemoSen↑, When in combination with 5-FU, itraconazole significantly reduced the proliferation rate of cancer cells.
TumCCA↑, itraconazole could regulate the G1-S transition and induce apoptosis of gastric cancer cells.
Apoptosis↑,
Gli1↓, expression of glioma-associated zinc finger transcription factor 1 (Gli1) was decreased at both transcriptional and translational levels after treatment with itraconazole.
TumCG↓, In vivo studies demonstrated that monotherapy with itraconazole by oral administration could inhibit the growth of xenografts, and that itraconazole could significantly enhance the antitumor efficacy of the chemotherapeutic agent 5-FU.
HH↓, Itraconazole regulates Hh signaling by inhibition of Gli1 transcription
Smo∅, Smo was unchanged in itraconazole-treated gastric cancer cells

8009-

itraC,

Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K/mTOR signaling pathways

vitro+vivo,

Melanoma,

SK-MEL-28

vitro+vivo,

Melanoma,

A375

OS↑, we find that itraconazole can inhibit melanoma growth and extend the survival of melanoma xenograft mice, compared to non-itraconazole-treated mice.
TumCP↓, itraconazole can significantly inhibit cell proliferation, as demonstrated by Ki-67 staining in itraconazole-treated tumor tissues
Ki-67↓,
TumCP↓, itraconazole inhibits the proliferation and colony formation of both SK-MEL-28 and A375 human melanoma cells.
Gli1↓, itraconazole significantly down-regulates Gli-1, Gli-2, Wnt3A, β-catenin and cyclin D1, while it up-regulates Gli-3 and Axin-1, indicating potent inhibitory effects of itraconazole on Hedgehog (Hh) and Wnt signaling pathways.
GLI2↓,
Wnt↓,
β-catenin/ZEB1↓,
cycD1/CCND1↓,
AXIN1↑,
GLI3↑,
AXIN1↑,
HH↓,
PI3K↓, itraconazole significantly suppresses the PI3K/mTOR signaling pathway
Akt↓,
*toxicity↓, mice under high doses of itraconazole (75 mg/kg or 100mg/kg) experienced some liver function impairments, as average levels of ALT and ALKP were slightly higher in these mice compared to mice with lower or no doses of itraconazole even though no stat

7994-

itraC,

From fungus fighter to cancer slayer: itraconazole as a multifaceted candidate for drug-resistant prostate cancer

Review,

Pca,

HH↓, ITZ reverses ABCB1-mediated docetaxel resistance, suppresses Hedgehog/GLI1 signaling, and inhibits cancer cell proliferation and invasion.
Gli1↓,
TumCP↓,
TumCI↓,
eff↑, Emerging evidence further suggests potential synergy with immune checkpoint inhibitors through tumor microenvironment modulation, though this remains unexplored in prostate cancer.

7993-

itraC,

Preclinical evaluation of itraconazole in docetaxel-resistant prostate cancer xenograft models

in-vivo,

Pca,

xenograft models

TumCG∅, Neither DTX alone, ITZ alone, nor their combination reduced primary tumour growth or cumulative tumour burden.
TumMeta↓, However, the combination suppressed development of lung micrometastases in both models
Ki-67↓, ITZ and DTX + ITZ reduced Ki-67 and Gli1 levels, demonstrating inhibition of proliferation and Hedgehog signalling despite the absence of tumour shrinkage
Gli1↓,
HH↓,

8001-

itraC,

Repurposing itraconazole as an anticancer agent

Review,

Var,

*AntiFungal↑, Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein,
AntiCan↑,
P-gp/ABCB1↓, itraconazole among patients with various types of cancer could not be explained by P-gp inhibition alone. R
HH↓, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/β-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions
mTOR↓,
Wnt↓,
β-catenin/ZEB1↓,
angioG↓,
LymphAG↓,
ChemoSen↑, survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer.
OS↑, 28 patients with biliary tract cancer received itraconazole, and subsequently experienced a median OS of 12 months
Gli1↓, Decreased GLI1 and Ki67 among vismodegib-naive 8 patients
Ki-67↓,
CSCs↓, Itraconazole may be a promising agent for targeting CSCs in relapsed disease of multiple types of cancer;

8015-

itraC,

Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth

vitro+vivo,

BCC,

HH↓, itraconazole, like other Hh pathway antagonists, can suppress Hh pathway activity and the growth of medulloblastoma in a mouse allograft model and does so at serum levels comparable to those in patients undergoing antifungal therapy.
Dose↝, itraconazole, was identified as a potent inhibitor of Hh pathway activity with an IC50 of approximately 800 nM
CYP51/14LDM↓, Itraconazole inhibits 14-α-lanosterol demethylase (14LDM), by a mechanism in which the triazole group of itraconazole coordinates the heme Fe2+ in the cytochrome P-450 active site of 14LDM
Gli1↓, The treated tumors showed decreased Gli1 mRNA levels, indicative of reduced Hh pathway activity

2179-

itraC,

Repurposing itraconazole for the treatment of cancer

Review,

Var,

HH↓, Figure 1
angioG↓,
TumCCA↑,
MDR1↓,
P-gp/ABCB1↓,
mTOR↓,
VEGF↓,
Smo↓,
Gli1↓,
OS↑, Itraconazole 400 mg daily was administered over 4 days every 2 weeks. A response rate of 44% was achieved, with a higher median overall survival time (1,047 days) compared with that previously reported in other studies, which ranged between 7-10mts
PSA↓, After the patient declined castration treatment, itraconazole was administered and the PSA level reduced by >50% in 3 months (300 mg twice daily)

34-

PFB,

Naturally occurring small-molecule inhibitors of hedgehog/GLI-mediated transcription

in-vitro,

PC,

PANC1

HH↓, 1, 9, 17, and 18 decreased Hh-related component expressions.
Gli1↓,
GLI2↓, We identified zerumbone (1), zerumbone epoxide (2), staurosporinone (9), 6-hydroxystaurosporinone (10), arcyriaflavin C (11) and 5,6-dihydroxyarcyriaflavin A (12) as inhibitors of GLI-mediated transcription.
PTCH1↓,
Bcl-2↓,

Showing Research Papers: 1 to 50 of 69
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 69

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1, Catalase↑, 1, GPx↑, 1, H2O2↓, 1, ROS↓, 2, SOD↑, 1,

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 1,

Immune & Inflammatory Signaling(tgid=16) ⓘ

Inflam↓, 2,

Functional Outcomes(tgid=23) ⓘ

cardioP↑, 1, hepatoP↑, 1, neuroP↑, 1, toxicity↓, 2,

Infection & Microbiome(tgid=24) ⓘ

AntiFungal↑, 1,
Total Targets: 13

Scientific Paper Hit Count for: Gli1, glioma-associated oncogene homolog 1

8 Glabrescione B
8 itraconazole
6 Curcumin
6 Resveratrol
6 EGCG (Epigallocatechin Gallate)
6 Sulforaphane (mainly Broccoli)
3 Apigenin (mainly Parsley)
3 Cynanbungeigenin C (CBC) and D (CBD)
3 Genistein (soy isoflavone)
3 Rosmarinic acid
2 Baicalein
2 Betulinic acid
1 Acoschimperoside P, 2’-acetate
1 Andrographis
1 Quercetin
1 Chemotherapy
1 Carvacrol
1 Thymol-Thymus vulgaris
1 Cyclopamine
1 Deguelin
1 Ellagic acid
1 Garcinol
1 Arsenic trioxide
1 Graviola
1 Germacranolide sesquiterpene lactone
1 Siegesbeckia glabrescens
1 Honokiol
1 Physalin F & B
1 salinomycin
1 Silymarin (Milk Thistle) silibinin
1 Saikosaponin B1 and D
1 Sutherlandioside D
1 Thymoquinone
1 Vitamin D3

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#:124  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

Gli1 Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned(tgid=0) ⓘ

Redox & Oxidative Stress(tgid=1) ⓘ

Mitochondria & Bioenergetics(tgid=3) ⓘ

Core Metabolism/Glycolysis(tgid=4) ⓘ

Cell Death(tgid=5) ⓘ

Kinase & Signal Transduction(tgid=6) ⓘ

Transcription & Epigenetics(tgid=7) ⓘ

Autophagy & Lysosomes(tgid=9) ⓘ

DNA Damage & Repair(tgid=10) ⓘ

Cell Cycle & Senescence(tgid=11) ⓘ

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

Migration(tgid=13) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Barriers & Transport(tgid=15) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Drug Metabolism & Resistance(tgid=21) ⓘ

Clinical Biomarkers(tgid=22) ⓘ

Functional Outcomes(tgid=23) ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress(tgid=1) ⓘ

Angiogenesis & Vasculature(tgid=14) ⓘ

Immune & Inflammatory Signaling(tgid=16) ⓘ

Functional Outcomes(tgid=23) ⓘ

Infection & Microbiome(tgid=24) ⓘ

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