HH Cancer Research Results

HH, Hedgehog signaling: Click to Expand ⟱

Source: CGL-CF

Type: HH

Sonic hedgehog, Shh; Indian hedgehog, Ihh; Desert hedgehog, Dhh ; Hh signaling pathway is able to regulate the EMT. Hh signaling-related factors, SHH, SMO and GLI1.
Hedgehog signaling is a crucial pathway in embryonic development and tissue homeostasis, but its dysregulation has been implicated in various cancers. The Hedgehog (Hh) pathway is activated by the binding of Hedgehog ligands (such as Sonic Hedgehog, Indian Hedgehog, and Desert Hedgehog) to their receptors, primarily Patched (PTCH) and Smoothened (SMO).

-Hedgehog pathway is crucial for the maintenance of stem cell populations. When deregulated, it can help sustain cancer stem cells (CSCs) that possess self-renewal properties, drive tumor recurrence, and confer resistance to conventional therapies.

-Inhibitors of the pathway, such as vismodegib and sonidegib, have been developed and are used in clinical settings, particularly for treating advanced BCC and other Hedgehog-dependent tumors.

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↓,

3383-

ART/DHA,

Dihydroartemisinin: A Potential Natural Anticancer Drug

Review,

Var,

TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

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

BBR,

Berberine, a natural compound, suppresses Hedgehog signaling pathway activity and cancer growth

vitro+vivo,

MB,

LS174T

HH↓, BBR significantly inhibited the Hh pathway activity.
Gli1∅, observations ruled out the possibility that BBR inhibited the Hh signaling pathway activity by targeting Gli.
PTCH1↓,
Smo↓, BBR inhibited the Hh pathway activity by targeting Smo,
TumCG↓, BBR inhibits the Hh-dependent medulloblastoma cell growth in vitro

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↓,

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

6254-

CBC/D,

Cynanchum auriculatum Royle ex Wight., Cynanchum bungei Decne. and Cynanchum wilfordii (Maxim.) Hemsl.: Current Research and Prospects

Review,

Var,

*neuroP↑, their dry roots as the bioactive part have been revealed to exhibit anti-tumor, neuroprotection, organ protection, reducing liver lipid and blood lipid, immunomodulatory, anti-inflammatory, and other activities
*Imm↑,
*Inflam↓,
CSCs↓, CA at the dosage of 10 mg/kg was demonstrated to inhibit proliferation and formation of breast cancer stem cells
HH↓, CB at the dosage of 50 mg/kg were revealed to block Hedgehog pathway-dependent medulloblastoma by regulating the level of Gli,
Gli↓,
AST↓, CA at the doses of 4 and 8 g/kg were able to decrease the levels of AST and ALT, improve SOD activity, and reduce malondialdehyde content in the in vivo
ALAT↓,
MDA↓,
hepatoP↑, 500 mg/kg was capable of reducing serum ALT and AST levels in mice with hepatic injury induced by CCl4, revealing its feasibility to exert hepatoprotection effect
*NRF2↑, protect them from oxidative toxicity and inflammatory damages by enhancing Nrf2 and HO-1 expression via the NF-κB signaling pathway
*HO-1↑,
NF-kB?, inhibitory protein of NF-κB
GSK‐3β↓, caudatin of CW during the dose of 12.5–50 μM was uncovered to inhibit GSK3β and β-catenin expression, which was attributed to the suppressive effect on wnt protein target genes COX-2, MMP2, and MMP9
β-catenin/ZEB1↓,
COX2↓,
MMP2↑,
MMP9↓,
BioAv↑, suggesting it could be absorbed and distributed rapidly without long-term accumulation in mice tissue

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↓,

3861-

CUR,

Curcumin as a novel therapeutic candidate for cancer: can this natural compound revolutionize cancer treatment?

Review,

Var,

*antiOx↑, fig 1
*Inflam↓,
PI3K↓, By inhibiting pro-survival and pro-inflammatory signaling cascades such as PI3K/Akt/mTOR, MAPK, Wnt/β-catenin, NF-κB, Hedgehog, Notch, and JAK/STAT3, curcumin effectively impedes cancer cell growth and promotes apoptosis.
Akt↓,
mTOR↓,
Wnt↓,
β-catenin/ZEB1↓,
NF-kB↓,
HH↓,
NOTCH↓,
JAK↓,
STAT3↓,
ADAM10↓, Curcumin may inhibit the function of the Notch pathway in cancer by inhibiting Notch pathway activators such as gamma secretases, Notch ligands, or ADAM10.

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↓,

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.

10-

CUR,

Curcumin Suppresses Lung Cancer Stem Cells via Inhibiting Wnt/β-catenin and Sonic Hedgehog Pathways

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

HH↓,
Wnt/(β-catenin)↓, curcumin suppressed the activation of both Wnt/β-catenin and Sonic Hedgehog pathways. T
Shh↓,
Smo↓,
Gli1↝,
GLI2↝,
CSCs↓, Curcumin Suppresses Lung Cancer Stem Cells via Inhibiting Wnt/β-catenin and Sonic Hedgehog Pathways
CD133↓, reduced number of CD133-positive cells, decreased expression levels of lung CSC markers,
CSCsMark↓,

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

6235-

CUSP9,

Exhaustive in vitro evaluation of the 9-drug cocktail CUSP9 for treatment of glioblastoma

in-vitro,

GBM,

tumCV↓,
NF-kB↓, disruption of cell survival pathways, including the NF-kB pathway,
HH↓, Itr-induced Hedgehog pathway inhibition could influence GBM cell proliferation and stem cell-like properties.
5HT↓, Ser, a serotonin uptake inhibitor

6237-

CUSP9,

CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide

NA,

GBM,

PI3K↓, ARTESUNATE phosphoinositide 3-kinase, Akt, increases ROS, NF-κB activation, TNF-alpha, IL-6, TLR2,
Akt↓,
ROS↑,
NF-kB↓,
TNF-α↓,
TLR2↓,
other↓, APREPITANT 10 hrs NK-1 receptors
TrxR↓, AURANOFIN 10 days thioredoxin, increases ROS, STAT3
STAT3↓,
MMPs↓, CAPTOPRIL 2 hrs ACE, AT1 receptors, MMPs
COX1↓, CELECOXIB 9 hrs COX-1 and -2, carbonic anhydrase -2 and -9
COX2↓,
CA↓,
ALDH↓, DISULFIRAM ALDH, increases ROS
P-gp↓, ITRACONAZOLE P-gp efflux transporters, BCRP, Hedgehog, 5-lipoxygenase
HH↓,
5LO↓,
mTOR↓, RITONAVIR P-gp efflux transporters [weak], Akt, mTOR, cyclin D3, proteasome,
CycD3↓,
Proteasome↓,
other↓, SERTRALINE Akt, mTOR, TCTP
MMP2↓, Captopril inhibited the activity of soluble MMP-2 and MMP-9
MMP9↓,
ALDH↓, Disulfiram potent inhibitor of all isoforms of aldehyde dehydrogenase, ALDH, disulfiram stops ethanol metabolism at the acetaldehyde stage
Copper↓, Since disulfiram chelates Cu++ in the stomach even without adding exogenous Cu

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

6249-

Cyc,

Cyclopamine tartrate, an inhibitor of Hedgehog signaling, strongly interferes with mitochondrial function and suppresses aerobic respiration in lung cancer cells

in-vitro,

NSCLC,

A549

in-vitro,

NSCLC,

H1299

HH↓, Cyclopamine was the first compound found to inhibit Hh signaling and has been invaluable for understanding the function of Hh signaling in development and cancer.
OCR↓, Our results showed that CycT, like glutamine depletion, caused a substantial decrease in oxygen consumption in a number of NSCLC cell lines,
TumCP↓, suppressed NSCLC cell proliferation, and induced apoptosis.
Apoptosis↑,
ROS↑, we found that CycT increased ROS generation, mitochondrial membrane hyperpolarization, and mitochondrial fragmentation, thereby disrupting mitochondrial function in NSCLC cells.
MMP↑, We found that CycT increases mitochondrial membrane potential substantially in NSCLC cells
mtDam↑,

6243-

Cyc,

Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened

Study,

Var,

AntiTum↑, The steroidal alkaloid cyclopamine has both teratogenic and antitumor activities arising from its ability to specifically block cellular responses to vertebrate Hedgehog signaling.
HH↓,
Smo↓, In principle, cyclopamine-mediated inhibition of vertebrate Smo activity could perturb any of these cellular events.

6244-

Cyc,

Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours

in-vivo,

Var,

xenograft tumours

HH↓, Hh pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist.
TumCG↓, Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumours in vivo.

6245-

Cyc,

Blockade of Hedgehog Signaling Inhibits Pancreatic Cancer Invasion and Metastases: A New Paradigm for Combination Therapy in Solid Cancers

vitro+vivo,

PC,

seven mice

HH↓, Hh inhibition with cyclopamine resulted in down-regulation of snail and up-regulation of E-cadherin, consistent with inhibition of epithelial-to-mesenchymal transition,
Snail↓,
E-cadherin↑,
EMT↓,
TumCI↓, striking reduction of in vitro invasive capacity
ChemoSen↑, Combination of gemcitabine and cyclopamine completely abrogated metastases while also significantly reducing the size of “primary” tumors.
TumMeta↓, Cyclopamine abrogates metastases in an orthotopic xenograft model of pancreatic cancer and synergizes with gemcitabine
ALDH↓, Cyclopamine treatment preferentially reduces the ALDH-expressing population in pancreatic cancer cells
eff↑, We believe that our results provide a compelling rationale for exploring Hh inhibitors in human pancreatic cancer, particularly from the standpoint of therapy of metastatic disease.

6246-

Cyc,

Cyclopamine is a novel Hedgehog signaling inhibitor with significant anti-proliferative, anti-invasive and anti-estrogenic potency in human breast cancer cells

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

HH↓, cyclopamine, a naturally occurring Hedgehog-specific small-molecule inhibitor, causes profound inhibition of tumor growth.
TumCP↓, cyclopamine displayed a significant potency in suppressing the proliferation of both estrogen-responsive (MCF-7) and estrogen-independent (MDA-MB-231) human breast cancer cells.
TumCCA↓, Cyclopamine induced a robust G1 cell cycle arrest and elicited notable effects on the expression of cyclin D1 through modulation of the MAPK/ERK signaling pathway.
TumCI↓, Cyclopamine also inhibited the invasive ability of both breast cancer cell lines by suppressing the expression levels of NF-κB, MMP2 and MMP9 protein
NF-kB↓,
MMP2↓,
MMP9↓,
ERα/ESR1↓, cyclopamine significantly downregulated the production of estrogen receptor-α protein.
cycD1/CCND1↓, expression level of cyclin D1 decreased in cyclopamine-treated cells.

6248-

Cyc,

The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

in-vitro,

CRC,

HH↓, We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis.
Apoptosis↑,
Slug↓, we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro.
Snail↓,
Twist↓,
EMT↓,
β-catenin/ZEB1↓, Cyclopamine Treatment Reduces β-Catenin-Related Transcription in the Colorectal Cancer Cell Line SW480 in a Dose-Dependent Manner
E-cadherin↑, Cyclopamine Treatment Induces the Expression of E-Cadherin in Both Benign and Malignant Colorectal Tumour-Derived Cell Lines and Reduces Invasion in SW480 Cells
TumCI↓,

6250-

Cyc,

Dose- and route-dependent teratogenicity, toxicity, and pharmacokinetic profiles of the hedgehog signaling antagonist cyclopamine in the mouse

in-vivo,

Nor,

mouse

*HH↓, cyclopamine is a potent Hh antagonist and is used experimentally both in vitro and in vivo to investigate the role of Hh signaling in diverse biological processes
*other↑, transient Hh signaling inhibition induces facial clefting anomalies in the mouse that mimic common human birth defects.

6251-

Cyc,

I only have eye for ewe: the discovery of cyclopamine and development of Hedgehog pathway-targeting drugs

Review,

Var,

HH↓, cyclopamine action remained enigmatic for 30 years, until this steroid alkaloid was found to be the first specific inhibitor of Hedgehog (Hh) signalling

6252-

Cyc,

Hedgehog Pathway Inhibitors as Targeted Cancer Therapy and Strategies to Overcome Drug Resistance

Review,

Var,

*BioAv↓, poor oral bioavailability, acid sensitivity, and some degrees of specificity of cyclopamine limit its therapeutic usage in clinical study
Smo↓, cyclopamine derivatives targeting SMO to inhibit the Hh signaling
HH↓,
eff↑, Vismodegib (GDC-0449, Erivedge®) has a higher potency and more favorable pharmaceutical properties than cyclopamine.

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↑,

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

33-

InA,

Inoscavin A, a pyrone compound isolated from a Sanghuangporus vaninii extract, inhibits colon cancer cell growth and induces cell apoptosis via the hedgehog signaling pathway

vitro+vivo,

Colon,

 xenograft mouse model.

HH↓, antitumor effects of Inoscavin A were related to the hedgehog (Hh) signaling pathway
Smo↓, Smo, the core receptor of the Hh pathway, was critical for the induction of apoptosis of Inoscavin A
TumCP↓, inhibiting Smo to suppress the activity of the Hh pathway though inhibiting cell proliferation and promoting apoptosis
Apoptosis↑,

2180-

itraC,

Repurposing Drugs in Oncology (ReDO)—itraconazole as an anti-cancer agent

Review,

Var,

Dose↝, generally it is used in the range 100 mg–600 mg daily, for between one to 30 days.
toxicity↝, ITZ is generally well-tolerated, though caution is advised with patients at high risk of heart failure or impaired hepatic function
BioAv↑, Bioavailability of ITZ is maximised by taking with food for the encapsulated form, or on an empty stomach for the oral solution.
Half-Life↝, produces an average peak plasma concentration of 239 ng/mL (0.34μM) within 4.5 hours
BioAv↑, mean absolute bioavailability is around 55%, and as a highly lipophilic molecule ITZ has a high affinity for tissues, achieving concentrations two to ten times higher than those in plasma
Dose↝, recommended, therefore, that for long-term treatment patients be regularly monitored for plasma levels
HH↓, identified ITZ as an inhibitor of the Hedgehog pathway at a clinically relevant concentration of 800 nM
TumAuto↑, Induction of autophagy is shown to be related to inhibition of the AKT-mTOR pathway, possibly related to ITZ-induced changes in cholesterol trafficking.
Akt↓,
mTOR↓,
angioG↓, Anti-angiogenic
MDR1↓, Reversal of multi-drug resistance
TumCP↓, ITZ inhibited proliferation, with an IC50 of 0.16 μM
eff↑, Combination therapy with cisplatin was superior to cisplatin monotherapy to a statistically significant extent (P ≤ 0.001 compared to ITZ or cisplatin alone) resulting in over 95% growth inhibition but no tumour regression.

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)

2177-

itraC,

Itraconazole improves survival outcomes in patients with colon cancer by inducing autophagic cell death and inhibiting transketolase expression

Study,

Colon,

present study analyzed extensive data from patients diagnosed with colon cancer using itraconazole between January 2011 and December 2015

in-vitro,

CRC,

COLO205

in-vitro,

CRC,

HCT116

OS↑, Itraconazole increases the 5-year survival rate in patients with late-stage colon cancer who receive chemotherapy
tumCV↓, itraconazole decreased the viability and cell colony formation, and induced cleaved caspase-3 expression and G1 cell cycle arrest of COLO 205 and HCT 116 cells.
Casp3↑,
TumCCA↑,
HH↓, Itraconazole can induce autophagic cell death by activating the hedgehog pathway to inhibit breast cancer cell proliferation (25).
TumAuto↑, expression levels of the autophagy-related proteins, LC3B and p62, significantly increased in COLO 205 and HCT 116 cells following treatment with itraconazole for 24 h
LC3B↑,
p62↑,
TKT↓, TKT expression was decreased following treatment with itraconazole in a time-dependent manner

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 64
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 64

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Catalase↑, 1, GPx↑, 1, H2O2↓, 1, HO-1↑, 1, NRF2↑, 1, ROS↓, 1, SOD↑, 1,

Transcription & Epigenetics ⓘ

other↑, 1,

Proliferation, Differentiation & Cell State ⓘ

HH↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Immune & Inflammatory Signaling ⓘ

Imm↑, 1, Inflam↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,

Functional Outcomes ⓘ

neuroP↑, 1, toxicity↓, 1,
Total Targets: 16

Scientific Paper Hit Count for: HH, Hedgehog signaling

10 Cyclopamine
8 Curcumin
6 Resveratrol
6 EGCG (Epigallocatechin Gallate)
4 Cynanbungeigenin C (CBC) and D (CBD)
3 Apigenin (mainly Parsley)
3 Genistein (soy isoflavone)
3 itraconazole
3 Sulforaphane (mainly Broccoli)
2 Quercetin
2 CUSP9
2 Glabrescione B
2 Rosmarinic acid
1 Acoschimperoside P, 2’-acetate
1 Andrographis
1 Artemisinin
1 Baicalein
1 Berberine
1 Betulinic acid
1 Deguelin
1 Ellagic acid
1 Germacranolide
1 Graviola
1 Siegesbeckia glabrescens
1 Inoscavin A
1 Physalin F & B
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#:141  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

HH Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

NA, unassigned ⓘ

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

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 ⓘ

Synaptic & Neurotransmission ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Transcription & Epigenetics ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

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