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,

Acoschimperoside P, 2'-acetate: a Hedgehog signaling inhibitory constituent from Vallaris glabra

in-vitro,

PC,

PANC1

 0.75–6uM

in-vitro,

Pca,

DU145

HH↓, Compound 1 was active in the assay for Hedgehog signaling inhibition.
PTCH1↓, The expression of GLI-related proteins (PTCH and BCL-2) in a dose-dependent manner was also inhibited by 1.
Bcl-2↓,
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↓,
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↓,
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.

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↓,

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.

16-

CP,

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

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

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↓,

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↓, 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↓,
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↓, 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,

MCF-7

 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.

30-

Ger,

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↓,

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.

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

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

2179-

itraC,

Repurposing itraconazole for the treatment of cancer

Review,

Var,

HH↓, Figure 1
angioG↓,
TumCCA↑,
MDR1↓,
P-gp↓,
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↓,

3079-

RES,

Therapeutic role of resveratrol against hepatocellular carcinoma: A review on its molecular mechanisms of action

Review,

Var,

angioG↓, Resveratrol suppresses angiogenesis and metastatic markers to reverse cancer spread.
TumMeta↓,
ChemoSen↑, Resveratrol chemosensitizes chemotherapy and synergizes anti-cancer phytochemicals.
NADPH↑, Both in vitro and in vivo studies indicates that resveratrol enhances various redox enzymes activity, especially nicotinamide adenine dinucleotide phosphate (NADPH)
SIRT1↑, resveratrol effectively modulates both the cytokine and chemokine profiles in immune and endothelial cells by the upregulation of sirtuin-1 (SIRT1)
NF-kB↓, suppression of NF-κB and prevention of the activation of NOD-like receptor family (Nrf) pyrin domain containing-3 inflammasome [
NLRP3↓,
Dose↝, The optimal dose of resveratrol being around 150 mg per day is considered safe by all means.
COX2↓, Cox2 ↓; MMP9 ↓
MMP9↓,
PGE2↓, Cox1 and 2; PGE2↓
TIMP1↑, Resveratrol suppresses the PMA-induced MMP activity in HepG2 cell line, while it also upregulates tissue inhibitor proteins of MMP, namely, TIMP1 and TIMP2, in dose-dependent manner
TIMP2↑,
Sp1/3/4↓, Resveratrol mitigates the expression of SP-1 by inhibiting both phosphorylation of JNK1/2 and expression of urokinase-type plasminogen activator in Huh-7 cell line
p‑JNK↓,
uPAR↓,
ROS↓, Resveratrol attenuates the excessive ROS production and inflammatory cytokine, IL-6, and CXCR4 receptor expression by downregulating Gli-1 expression.
CXCR4↓,
IL6↓,
Gli1↓,
*ROS↓, redox imbalance may be attenuated by resveratrol via downregulating ROS production and simultaneously inducing antioxidant enzymes, GST, SOD, CAT and GPx activities in the cells
*GSTs↑,
*SOD↑,
*Catalase↑,
*GPx↑,
*lipid-P↓, [72] observed that resveratrol treatment not only reduces lipid peroxidation but also increases GSH and GST serum levels in CCl4-treated rats as compared to the CCl4-control animals
*GSH↑,
eff↑, Resveratrol, in combination with thymoquinone (TQ), has been demonstrated to provide a synergistic antiproliferative efficacy against HCC cell lines as reported by Ismail et al.
eff↑, Curcumin, a potential anticancer phytochemical, in combination with resveratrol has been reported to trigger synergistic apoptotic effects against Hepa1–6 cells
eff↑, berberine in combination with resveratrol lowers the cell viability and cell adhesion. At low concentration, berberine significantly induces cell death while resveratrol inhibits cell migration in HepG2 cells

3098-

RES,

Regulation of Cell Signaling Pathways and miRNAs by Resveratrol in Different Cancers

Review,

Var,

NOTCH2↓, resveratrol has been reported to target multiple proteins in ovarian cancer, markedly reducing NOTCH2 and HES1 in OVCAR-3 and CAOV-3 cells
Wnt↓, In CAOV-3 cells, resveratrol downregulated WNT2 and reduced the nuclear accumulation of β-catenin
β-catenin/ZEB1↓,
p‑SMAD2↓, Resveratrol effectively inhibits SMAD proteins
p‑SMAD3↓, Resveratrol has been reported to reduce phosphorylated-SMAD2/3 in colorectal cancer LoVo cells
PTCH1↓, PTCH, SMO, and GLI-1 were also inhibited in resveratrol-treated colorectal cancer HCT116 cells
Smo↓,
Gli1↓,
E-cadherin↑, resveratrol upregulated E-cadherin
NOTCH⇅, Although some reports document efficient inhibition of different proteins of the NOTCH pathway by resveratrol to inhibit cancer, there are conflicting reports that resveratrol can activate the NOTCH pathway, leading to its anticancer activity.
TAC?,
NKG2D↑, Resveratrol has been found to increase the cell-surface expression of NKG2D ligands and DR4 along
DR4↑,
survivin↓, Resveratrol dose-dependently downregulated survivin in HepG2 cells.
DR5↑, resveratrol upregulated DR4, DR5, Bax, and p27(/KIP1) and inhibited the expression of cyclin D1 and Bcl-2
BAX↑,
p27↑,
cycD1/CCND1↓,
Bcl-2↓,
STAT3↓, Resveratrol exerts inhibitory effects on the constitutive activation of STAT3 and STAT5.
STAT5↓,
JAK↓, Resveratrol has also been shown to prevent the activation of JAK,
DNAdam↑, Resveratrol induced DNA damage, as evidenced by the presence of multiple γ-H2AX foci after treatment with 25 μM resveratrol.
γH2AX↑,

101-

RES,

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

in-vitro,

GC,

SGC-7901

 10 uM

HH↓, resveratrol was able to inhibit the Hh signaling pathway and EMT, and suppress invasion and metastasis in gastric cancer in vitro.
Gli1↓, decrease in Gli-1, Snail and N-cadherin expression, and an increase in E-cadherin expression in the resveratrol and cyclopamine group compared with the control group
EMT↓,
Snail↓,
N-cadherin↓,
E-cadherin↑,
TumCI↓, resveratrol was able to inhibit the Hh signaling pathway and EMT, and suppress invasion and metastasis in gastric cancer in vitro.
TumMeta↓,

4663-

RES,

Exploring resveratrol’s inhibitory potential on lung cancer stem cells: a scoping review of mechanistic pathways across cancer models

Review,

Var,

*antiOx↑, Resveratrol is a natural compound with notable health benefits, such as anti-inflammatory, antioxidant, and chemopreventive properties.
*Inflam↓,
*chemoPv↑,
CSCs↓, It has shown potential in inhibiting tumorigenesis and tumour progression via targeted therapy, specifically by targeting cancer stem cells (CSCs)
Wnt↓, Three papers reported on the effects on resveratrol on Wnt/ β-catenin pathway
β-catenin/ZEB1↓,
NOTCH↓, 3 papers on Notch pathway
PI3K↓, 3 papers on PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
GSK‐3β↝, Akt/GSK β/snail pathway
Snail↓,
HH↓, 4 papers on Hedgehog pathway
p‑GSK‐3β↓, It downregulated p-AKT, p-GSK3β, Snail and N-cadherin in a dose-dependent manner, indicating its role in modulating the Akt/GSK3β/snail signalling pathway to reverse EMT
N-cadherin↓,
EMT↓,
CD133↓, This further reduced CSC markers CD133, CD44, ALDH1A1, OCT4, SOX2 and β-catenin
CD44↓,
ALDH1A1↓,
OCT4↓,
SOX4↓,
Shh↓, Sun et al., reported that resveratrol downregulated SHH, SMO, Gli1 and Gli2 proteins on renal CSC, reducing the number and size of renal cancer cell spheres and decreasing expression of stemness markers CD44 and CD133
Smo↓,
Gli1↓,
GLI2↓,

1748-

RosA,

The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity

Review,

Var,

AntiCan↑, RA exhibits significant potential as a natural agent for cancer prevention and treatment
*BioAv↝, Various factors, including its lipophilic nature, stability in the gastrointestinal tract, and interactions with food, can significantly influence its absorption
*CardioT↓, RA attenuated these effects by reducing ROS levels, indicating its potential role as a cardioprotective agent during chemotherapy.
*Iron↓, Another significant mechanism antioxidant activity of RA is its capacity to chelate transition metal ions, particularly iron (Fe2+) and copper (Cu2+), which can catalyze the formation of highly reactive hydroxyl radicals through the Fenton reaction.
*ROS↓, forming stable complexes with Fe2+ and Cu2+, thus inhibiting their pro-oxidant activity.
*SOD↑, SOD, CAT, and GPx, play crucial roles in neutralizing ROS and maintaining cellular redox homeostasis. RA upregulates the expression and activity of these enzymes
*Catalase↑,
*GPx↑,
*NRF2↑, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a primary regulator of the antioxidant response
MARK4↓, Anwar’s study demonstrated that RA inhibited MARK4 activity in MDA-MB-231 breast cancer cells, resulting in dose-dependent apoptosis
MMP9↓, RA effectively inhibited cancer cell invasion and migration by reducing matrix metalloproteinase-9 (MMP-9) activity
TumCCA↑, caused cell cycle arrest
Bcl-2↓, RA downregulates Bcl-2 expression and upregulates Bax, thereby promoting apoptosis
BAX↑,
Apoptosis↑,
E-cadherin↑, promoting E-cadherin expression, while downregulating N-cadherin and vimentin
N-cadherin↓,
Vim↓,
Gli1↓, induced apoptosis by downregulating Gli1, a key component of the Hedgehog signaling pathway,
HDAC2↓, RA induced apoptosis by modulating histone deacetylase 2 (HDAC2) expression
Warburg↓, anti-Warburg effect of RA in colorectal carcinoma
Hif1a↓, RA inhibits hypoxia-inducible factor-1 alpha (HIF-1α) and downregulates miR-155
miR-155↓,
p‑PI3K↑, RA has been shown to upregulate p-PI3K, protecting cells through the PI3K/Akt pathway,
ROS↑, RA, induces significant ROS generation in A549 cells, which triggers both apoptosis and autophagy.
*IronCh↑, RA’s dual nature as both a phenolic acid and a flavonoid-related compound enables it to chelate metal ions and prevent the formation of free radicals,

3010-

RosA,

Exploring the mechanism of rosmarinic acid in the treatment of lung adenocarcinoma based on bioinformatics methods and experimental validation

in-vitro,

Lung,

A549

in-vivo,

NA,

TumCG↓, RosA could inhibit the growth of transplanted tumors in nude mice bearing tumors of lung cancer cells, reduce the positive expression of Ki67 in lung tumor tissue, and hinder the proliferation of lung tumor cells.
Ki-67↓,
FABP4↑, Upregulated expression of PPARG and FABP4 by activating the PPAR signaling pathway increases the level of ROS in lung tumor tissues and promotes apoptosis of lung tumor cells.
PPARα↑,
ROS↑, RosA increases ROS levels in lung tumor tissues and induces apoptosis
Apoptosis↑,
MMP9↓, In addition, RosA can also reduce the expression of MMP-9 and IGFBP3, inhibit the migration and invasion of lung tumor tissue cells.
IGFBP3↓,
MMP2↓, In addition, RosA down-regulated the expression of MMP-9 and MMP2, regulated epithelial-mesenchymal transition to inhibit cell invasion, and slow down tumor development.
EMT↓,
TumCI↓,
PI3K↓, his study also confirmed that RosA down-regulated the expression of the PI3K/AKT/mTOR pathway-related proteins
Akt↓,
mTOR↓,
Gli1↓, Xiang Zhou et al. [28] reported that RosA inhibited the growth of PDAC tumors by inhibiting Gli1.
PPARγ↑, Upregulated expression of PPARG
Cyt‑c↑, figure 7

3035-

RosA,

Rosmarinic Acid Decreases the Malignancy of Pancreatic Cancer Through Inhibiting Gli1 Signaling

in-vitro,

PC,

in-vivo,

NA,

Gli1↓, RA dramatically down-regulated Gli1 and its downstream targets
TumCCA↑, RA induced G1/S cell cycle arrest and apoptosis in the PDAC cells through regulating the expression of P21, P27, CDK2, Cyclin E, Bax, and Bcl-2, it inhibited the PDAC cell migration and invasion via E-cadherin and MMP-9.
TumCMig↓,
TumCI↓,
CDK2↓,
cycE/CCNE↓,
P21↑,
p27↑,

4900-

Sal,

Anticancer Mechanisms of Salinomycin in Breast Cancer and Its Clinical Applications

Review,

BC,

CSCs↓, Salinomycin, a monocarboxylic polyether antibiotic isolated from Streptomyces albus, can precisely kill cancer stem cells (CSCs), particularly BCSCs, by various mechanisms, including apoptosis, autophagy, and necrosis.
Apoptosis↑,
TumAuto↑,
necrosis↑,
TumCP↓, salinomycin can inhibit cell proliferation, invasion, and migration in BC and reverse the immune-inhibitory microenvironment to prevent tumor growth and metastasis.
TumCI↓,
TumCMig↓,
TumCG↓,
TumMeta↓,
eff↑, Salinomycin is over 100 times more effective against BCSCs than paclitaxel, the traditional chemotherapy drug for the treatment of BC
Bcl-2↓, downregulation of Bcl-2 expression, and decreases their migration capacity, which is accompanied by downregulation of c-Myc and Snail expression
cMyc↓,
Snail↓,
ALDH↓, salinomycin reduces aldehyde dehydrogenase activity and the expression of MYC, AR, and ERG; it induces oxidative stress and inhibits nuclear factor (NF)-κB activity
Myc↓,
AR↓,
ROS↑, Salinomycin also induces autophagy by increasing intracellular ROS level, which is accompanied by MAPK signaling pathway activation
NF-kB↓,
PTCH1↓, significantly reduces tumor growth, which is accompanied by decreased PTCH, SMO, Gli1, and Gli2 expression
Smo↓,
Gli1↓,
GLI2↓,
Wnt↓, Figure 2
mTOR↓,
GSK‐3β↓,
cycD1/CCND1↓,
survivin↓,
P21↑,
p27↑,
CHOP↑,
Ca+2↑, cytosolic
DNAdam↑,
Hif1a↓,
VEGF↓,
angioG↓,
MMP↓, salinomycin can affect the cell membrane potential and reduce the level of ATP to induce mitophagy and mitoptosis.
ATP↓,
p‑P53↑, Salinomycin increases DNA breaks in BC cells as well as the expression of phosphorylated p53 and γH2AX in Hs578T cells.
γH2AX↑,
ChemoSen↑, Table 3 Synergistic anticancer co-action of salinomycin with other agents in BC.

3197-

SFN,

Sulforaphane Inhibits Self-renewal of Lung Cancer Stem Cells Through the Modulation of Polyhomeotic Homolog 3 and Sonic Hedgehog Signaling Pathways

in-vitro,

Lung,

A549

in-vitro,

Lung,

H460

TumCP↓, SFN inhibited the proliferation of lung cancer cells and lung cancer stem cells simultaneously.
CSCs↓,
Shh↓, SFN inhibited the activity of PHC3 and SHH signaling pathways in the lung cancer stem cells
Smo↓, SFN can obviously reduce the mRNA and protein expression of ShhSmo and Gli1 in CD133-positive cells as compared to CD133-negative cells
Gli1↓,

110-

SFN,

Sulforaphane regulates self-renewal of pancreatic cancer stem cells through the modulation of Sonic hedgehog-GLI pathway

in-vivo,

PC,

 20 mg/kg

 mice

HH↓, Hedgehog pathway blockade by SFN at a dose of 20 mg/kg resulted in a 45 % reduction in growth of pancreatic cancer tumors and reduced expression of Shh pathway components, Smo, Gli 1, and Gli 2 in mouse tissues.
Smo↓,
Gli1↓,
GLI2↓,
Shh↓,
VEGF↓, SFN inhibited the expression of pluripotency maintaining transcription factors Nanog and Oct-4 and angiogenic markers VEGF and PDGFRα which are downstream targets of Gli transcription
PDGFRA↓,
EMT↓, SFN treatment resulted in a significant reduction in EMT markers Zeb-1, which correlated with increase in E-Cadherin expression suggesting the blockade of signaling involved in early metastasis.
Zeb1↓,
Bcl-2↓, SFN downregulated the expression of Bcl-2 and XIAP to induce apoptosis.
XIAP↓,
E-cadherin↑,
OCT4↓,
Nanog↓,
TumCG↑, SFN results in marked reduction in EMT, metastatic, angiogenic markers with significant inhibition in tumor growth in mice.

111-

SFN,

Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling

in-vitro,

BC,

SUM159

 TNBC

HH↓, suppression of Hh/Gli1 signaling by sulforaphene may reduce the MMP-2 and MMP-9 activities and cellular invasiveness of human breast cancer cells
Gli1↓,
MMP2↓,
MMP9↓,
Smo↓, Sulforaphene Inhibited the Expression of Hh Signaling Effectors, Smo and Gli1,
TumCMig↓, Hh Signaling Regulated the Migration and Invasion of SUM159 Human Breast259 Cancer Cells via Reducing the MMP Expression.
TumCI↓,

2448-

SFN,

Sulforaphane and bladder cancer: a potential novel antitumor compound

Review,

Bladder,

Apoptosis↑, Recent studies have demonstrated that Sulforaphane not only induces apoptosis and cell cycle arrest in BC cells, but also inhibits the growth, invasion, and metastasis of BC cells
TumCG↓,
TumCI↓,
TumMeta↓,
glucoNG↓, Additionally, it can inhibit BC gluconeogenesis
ChemoSen↑, demonstrate definite effects when combined with chemotherapeutic drugs/carcinogens.
TumCCA↑, SFN can block the cell cycle in G2/M phase, upregulate the expression of Caspase3/7 and PARP cleavage, and downregulate the expression of Survivin, EGFR and HER2/neu
Casp3↑,
Casp7↑,
cl‑PARP↑,
survivin↓,
EGFR↓,
HER2/EBBR2↓,
ATP↓, SFN inhibits the production of ATP by inhibiting glycolysis and mitochondrial oxidative phosphorylation in BC cells in a dose-dependent manner
Glycolysis↓,
mt-OXPHOS↓,
AKT1↓, dysregulation of glucose metabolism by inhibiting the AKT1-HK2 axis
HK2↓,
Hif1a↓, Sulforaphane inhibits glycolysis by down-regulating hypoxia-induced HIF-1α
ROS↑, SFN can upregulate ROS production and Nrf2 activity
NRF2↑,
EMT↓, inhibiting EMT process through Cox-2/MMP-2, 9/ ZEB1 and Snail and miR-200c/ZEB1 pathways
COX2↓,
MMP2↓,
MMP9↓,
Zeb1↓,
Snail↓,
HDAC↓, FN modulates the histone status in BC cells by regulating specific HDAC and HATs,
HATs↓,
MMP↓, SFN upregulates ROS production, induces mitochondrial oxidative damage, mitochondrial membrane potential depolarization, cytochrome c release
Cyt‑c↓,
Shh↓, SFN significantly lowers the expression of key components of the SHH pathway (Shh, Smo, and Gli1) and inhibits tumor sphere formation, thereby suppressing the stemness of cancer cells
Smo↓,
Gli1↓,
BioAv↝, SFN is unstable in aqueous solutions and at high temperatures, sensitive to oxygen, heat and alkaline conditions, with a decrease in quantity of 20% after cooking, 36% after frying, and 88% after boiling
BioAv↝, It has been reported that the ability of individuals to use gut myrosinase to convert glucoraphanin into SFN varies widely
Dose↝, Excitingly, it has been reported that daily oral administration of 200 μM SFN in melanoma patients can achieve plasma levels of 655 ng/mL with good tolerance

1731-

SFN,

Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts

Review,

Var,

CSCs↓, A number of studies have indicated that sulforaphane may target CSCs
ChemoSen↑, Combination therapy with sulforaphane and chemotherapy in preclinical settings has shown promising results.
NF-kB↓, downregulation of NF-kB activity by sulforaphane
Shh↓, Inhibits SHH pathway (Smo, Gli1, Gli2)
Smo↓,
Gli1↓,
GLI2↓,
PI3K↓, Inhibits PI3K/AKT pathway
Wnt↓, Inhibits Wnt/b-catenin pathway
β-catenin/ZEB1↓,
Nanog↓, sulforaphane was found to reduce the expression of SHH pathway components, as well as downstream target genes (e.g.,Nanog, Oct-4, VEGF and ZEB-1)
COX2↓, han et al. suggested that sulforaphane inhibited the EMT process via the COX-2/MMP2,9/ZEB1, Snail and miR-200c/ZEB1 pathways,
Zeb1↓,
Snail↓,
ChemoSideEff↓, More importantly, the combination therapy abolished tumor-initiating potential in vivo, without inducing additional side effects
eff↑, Broccoli sprouts contain approximately 20-times more glucoraphanin than broccoli, which represents typically 74% of all glucosinolates in the sprouts
*BioAv↑, Again, the bioavailability of sulforaphane from broccoli sprouts or broccoli sprout preparations heavily relies on the presence of plant myrosinase.

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↑,

109-

SIL,

Silibinin induces apoptosis through inhibition of the mTOR-GLI1-BCL2 pathway in renal cell carcinoma

vitro+vivo,

RCC,

769-P

in-vitro,

RCC,

786-O

in-vitro,

RCC,

ACHN

in-vitro,

RCC,

OS-RC-2

 (50-200 uM) 200mg/kg vivo

HH↓,
Gli1↓, downregulation of GLI1 and BCL2,
GLI2↓, silibinin induces apoptosis of RCC cells through inhibition of the mTOR-GLI1‑BCL2 pathway.
mTOR↓,
Bcl-2↓,
Apoptosis↑, Silibinin induces the apoptosis of RCC cells involving activation of caspase-3 and PARP
Casp3↑,
PARP↑,
TumCG↓, Silibinin inhibits the growth of RCC xenografts in vivo

Showing Research Papers: 1 to 50 of 54
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 54

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Catalase↑, 3, GPx↑, 3, GSH↑, 1, GSTs↑, 1, H2O2↓, 1, Iron↓, 1, lipid-P↓, 1, NRF2↑, 1, ROS↓, 3, SOD↑, 3,

Metal & Cofactor Biology ⓘ

IronCh↑, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↑, 1, BioAv↝, 1,

Functional Outcomes ⓘ

cardioP↑, 1, CardioT↓, 1, chemoPv↑, 1, hepatoP↑, 1, neuroP↑, 1, toxicity↓, 1,
Total Targets: 22

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

6 Resveratrol
6 Curcumin
6 EGCG (Epigallocatechin Gallate)
6 Sulforaphane (mainly Broccoli)
3 Apigenin (mainly Parsley)
3 Genistein (soy isoflavone)
3 Rosmarinic acid
2 Baicalein
2 Betulinic acid
2 Cynanbungeigenin C (CBC) and D (CBD)
2 Glabrescione B
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 Germacranolide
1 Graviola
1 Siegesbeckia glabrescens
1 itraconazole
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 ⓘ

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Metal & Cofactor Biology ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

Home Page