Shh Cancer Research Results

Shh, sonic hedgehog: Click to Expand ⟱

Source:

Type: Hedgehog

Components of Shh pathway (smoothened, patched, Gli1 and Gli2).
Sonic Hedgehog (SHH) is a key signaling protein involved in various developmental processes, including cell growth, differentiation, and tissue patterning. The SHH signaling pathway is crucial during embryonic development, but its dysregulation can lead to several types of cancer.
The SHH pathway is activated when the SHH protein binds to its receptor, Patched (PTCH). This interaction relieves the inhibition of another protein, Smoothened (SMO), leading to the activation of downstream signaling that promotes cell proliferation and survival.

In many cancers, SHH and its downstream signaling components are often overexpressed. This overexpression can lead to increased cell proliferation, survival, and tumor growth.

Scientific Papers found: Click to Expand⟱

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

2290-

Ba,

Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer

Review,

GI,

p‑mTOR↓, Baicalein treatment decreased the expression levels of p-mTOR, p-Akt, p-IκB and NF-κB proteins, and suppressed GC cells by inhibiting the PI3K/Akt
p‑Akt↓,
p‑IKKα↓,
NF-kB↓,
PI3K↓,
Akt↓,
ROCK1↓, Baicalin reduces HCC proliferation and metastasis by inhibiting the ROCK1/GSK-3β/β-catenin signaling pathway
GSK‐3β↓,
CycB/CCNB1↓, Baicalein induces S-phase arrest in gallbladder cancer cells by down-regulating Cyclin B1 and Cyclin D1 in gallbladder cancer BGC-SD and SGC996 cells while up-regulating Cyclin A
cycD1/CCND1↓,
cycA1/CCNA1↑,
CDK4↓, Following baicalein treatment, there is a down-regulation of Ezrin, CyclinD1, and CDK4, as well as an up-regulation of p53 and p21 protein levels, thereby leading to the induction of CRC HCT116 cell cycle arrest
P53↑,
P21↑,
TumCCA↑,
MMP2↓, baicalein was able to inhibit the metastasis of gallbladder cancer cells by down-regulating ZFX, MMP-2 and MMP-9.
MMP9↓,
EMT↓, Baicalein treatment effectively inhibits the snail-induced EMT process in CRC HT29 and DLD1 cells
Hif1a↓, Baicalein inhibits VEGF by downregulating HIF-1α, a crucial regulator of angiogenesis
Shh↓, baicalein inhibits the metastasis of PC by impeding the Shh pathway
PD-L1↓, Baicalin and baicalein down-regulate PD-L1 expression induced by IFN-γ by reducing STAT3 activity
STAT3↓,
IL1β↓, baicalein therapy significantly diminishes the levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), IL-2, IL-6, and GM-CSF
IL2↓,
IL6↓,
PKM2↓, Baicalein, by reducing the expression levels of HIF-1A and PKM2, can inhibit the glycolysis process in ESCC cells
HDAC10↓, Baicalein treatment increases the level of miR-3178 and decreases HDAC10 expression, resulting in the inactivation of the AKT signaling pathways.
P-gp↓, baicalein reverses P-glycoprotein (P-gp)-mediated resistance in multidrug-resistant HCC (Bel7402/5-FU) cells by reducing the levels of P-gp and Bcl-xl
Bcl-xL↓,
eff↓, Baicalein combined with gemcitabine/docetaxel promotes apoptosis of PC cells by activating the caspase-3/PARP signaling pathway
BioAv↓, baicalein suffers from low water solubility and susceptibility to degradation by the digestive system
BioAv↑, Encapsulation of baicalein into liposomal bilayers exhibits a therapeutic efficacy close to 90% for PDAC

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

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↓,

4671-

CUR,

Targeting colorectal cancer stem cells using curcumin and curcumin analogues: insights into the mechanism of the therapeutic efficacy

in-vitro,

CRC,

CSCs↓, Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth.
TumCG↓,
ChemoSen↑, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy,
Wnt↓, Three major signaling pathways in which curcumin plays a pivotal role in CSC self-renewal behavior are the Wnt/β-catenin, Sonic Hedgehog (SHH), and Notch pathways
β-catenin/ZEB1↓,
Shh↓,
NOTCH↓,
DNMT1↓, Figure 1
STAT3↓,
NF-kB↓,
EGFR↓,
IGFR↓,
TumCCA↓,
cl‑PARP↑,
BAX↑,
ECM/TCF↓,

1607-

EA,

Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions

Review,

GC,

STAT3↓, EA inhibits STAT3 signaling
TumCP↓, EA inhibits cell proliferation, induces apoptosis
Apoptosis↑,
NF-kB↓, inhibiting nuclear factor-kappa B
EMT↓, suppressing epithelial–mesenchymal transition
RadioS↑, In liver cancer, EA exhibits radio-sensitizing effects
antiOx↑, As a potential antioxidant agent,
COX1↓, EA suppresses the expression of several factors, including COX1, COX2, c-myc, snail, and twist1
COX2↓,
cMyc↓,
Snail↓,
Twist↓,
MMP2↓, significantly decreased MMP-2 and MMP-9 expression and activity.
P90RSK↓,
CDK8↓, downregulate CDK8 expression and activity
PI3K↓, inactivating PI3K/Akt signaling
Akt↓,
TumCCA↑, promote cell cycle arrest
Casp8↑, ctivating caspase-8, and lowering proliferating cell nuclear antigen (PCNA) expression,
PCNA↓,
TGF-β↓,
Shh↓, suppression of the Akt, Shh, and Notch pathways, EA can prevent the growth, angiogenesis, and metastasis of pancreatic cancer
NOTCH↓,
IL6↓,
ALAT↓, decreasing liver injury biomarkers such as alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST)
ALP↓,
AST↓,
VEGF↓,
P21↑,
*toxicity∅, no toxicity was found for a 50% effective dose by the intraperitoneal route inferior to 1 mg/kg/day
*Inflam↓, ncluding anti-inflammatory [10], anti-oxidant [11], anti-allergic [12], and anti-mutagenic [13] properties, as well as potential health advantages like gastroprotective [14], cardioprotective [15], neuroprotective [16, 17], and hepatoprotective [18,
*cardioP↑,
*neuroP↑,
*hepatoP↑,
ROS↑, Exposure to EAs induced apoptosis, accelerated cell cycle arrest, and elevated the generation of reactive oxygen intermediates [59].
*NRF2↓, As a potential antioxidant agent, it scavenges reactive oxygen species (ROS), and by upregulating of Nrf2,
*GSH↑, Moreover, EA increases reduced glutathione (GSH), which is critical for cellular defense against oxidative stress and liver damage,

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

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

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↓,

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

2868-

HNK,

Honokiol: A review of its pharmacological potential and therapeutic insights

Review,

Var,

Review,

Sepsis,

*P-gp↓, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6),
*ROS↓,
*TNF-α↓,
*IL10↓,
*IL6↓,
eIF2α↑, Bcl-2, phosphorylated eIF2Î±, CHOP,GRP78, Bax, cleaved caspase-9 and phosphorylated PERK
CHOP↑,
GRP78/BiP↑,
BAX↑,
cl‑Casp9↑,
p‑PERK↑,
ER Stress↑, endoplasmic reticulum stress and proteins in apoptosis in 95-D and A549 cells
Apoptosis↑,
MMPs↓, decrease in levels of matrix metal-mloproteinases, P-glycoprotein expression, the formation of mammosphere, H3K27 methyltransferase, c-FLIP, level of CXCR4 receptor,pluripotency-factors, Twist-1, class I histone deacetylases, steroid receptor co
cFLIP↓,
CXCR4↓,
Twist↓,
HDAC↓,
BMPs↑, enhancement in Bax protein, and (BMP7), as well as interference with an activator of transcription 3 (STAT3), (mTOR), (EGFR), (NF-kB) and Shh
p‑STAT3↓, secreased the phosphorylation of STAT3
mTOR↓,
EGFR↓,
NF-kB↓,
Shh↓,
VEGF↓, induce apoptosis, and regulate the vascular endothelial growth factor-A expression (VEGF-A)
tumCV↓, human glioma cell lines (U251 and U-87 MG) through inhibition of colony formation, glioma cell viability, cell migration, invasion, suppression of ERK and AKT signalling cascades, apoptosis induction, and reduction of Bcl-2 expression.
TumCMig↓,
TumCI↓,
ERK↓,
Akt↓,
Bcl-2↓,
Nestin↓, increased the Bax expression, lowered the CD133, EGFR, and Nesti
CD133↓,
p‑cMET↑, HKL through the downregulating the phosphorylation of c-Met phosphorylation and stimulation of Ras,
RAS↑,
chemoP↑, Cheng and coworker determined the chemopreventive role of HKL against the proliferation of renal cell carcinoma (RCC) 786â0 cells through multiple mechanism
*NRF2↑, , HKL also effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in in vivo and in vitro model
*NADPH↓, (HUVECs) such as inhibition of NADPH oxidase activity, suppression of p22 (phox) protein expression, Rac-1 phosphorylation, reactive oxygen species production, inhibition of degradation of Ikappa-B-alpha, and suppression of activity of of NF-kB
*p‑Rac1↓,
*ROS↓,
*IKKα↑,
*NF-kB↓,
*COX2↓, Furthermore, HKL treatment the inhibited cyclooxygenase (COX-2) upregulation, reduces prostaglandin E2 production, enhanced caspase-3 activity reduction
*PGE2↓,
*Casp3↓,
*hepatoP↑, compound also displayed hepatoprotective action against oxidative injury in tert-butyl hydroperoxide (t-BHP)-injured AML12 liver cells in in vitro model
*antiOx↑, compound reduces the level of acetylation on SOD2 to stimulate its antioxidative action, which results in reduced reactive oxygen species aggregation in AML12 cells
*GSH↑, HKL prevents oxidative damage induced by H2O2 via elevating antioxidant enzymes levels which includes glutathione and catalase and promotes translocation and activation transcription factor Nrf2
*Catalase↑,
*RenoP↑, imilarly, the compound protects renal reperfusion/i-schemia injury (IRI) in adult male albino Wistar rats via reducing theactivities of serum alkaline phosphatase (ALP), aspartate aminotrans- ferase (AST) and alanine aminotransferase (ALT)
*ALP↓,
*AST↓,
*ALAT↓,
*neuroP↑, Several reports and works have shown that HKL displays some neuroprotective properties
*cardioP↑, Cardioprotection
*HO-1↑, the expression level of heme oxygenase-1 (HO-1)was remarkably up-regulated and miR-218-5p was significantly down-regulated in septic mice treated with HKL
*Inflam↓, anti-inflammatory action of HKL at dose of 10 mg/kg in the muscle layer of mice

66-

QC,

Emerging impact of quercetin in the treatment of prostate cancer

Review,

Pca,

CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, Inhibitory effects of quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt/(β-catenin)↓, wnt
PSA↓,
VEGF↓,
PARP↑,
Casp3↑,
Casp9↑,
DR5↑,
ROS⇅,
Shh↓,
P53↑, figure 1
P21↑, quercetin regulates p21 expression
EGFR↓,
TumCCA↑, quercetin has cell-specific anti-proliferative impacts via stimulation of cell cycle arrest at the G1 stage.
ROS↑, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↓,
TumCP↓,
selectivity↑, In breast cancer cells, quercetin inhibits cell proliferation without exerting any cytotoxic impact on normal breast epithelium
PDGF↓, figure 1
EGF↓,
TNF-α↓,
VEGFR2↓,
mTOR↓,
cMyc↓,
MMPs↓,
GRP78/BiP↑,
CHOP↑,

3369-

QC,

Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects

Review,

Pca,

FAK↓, Quercetin can inhibit HGF-induced melanoma cell migration by inhibiting the activation of c-Met and its downstream Gabl, FAK and PAK [84]
TumCCA↑, stimulation of cell cycle arrest at the G1 stage
p‑pRB↓, mediated through regulation of p21 CDK inhibitor and suppression of pRb phosphorylation resulting in E2F1 sequestering.
CDK2↑, low dose of quercetin has brought minor DNA injury and Chk2 induction
CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt↓,
ROS↑, colorectal cancer, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↑,
Akt↓, Figure 1 anti-cancer mechanisms
NF-kB↓,
FasL↑,
Bak↑,
BAX↑,
Bcl-2↓,
Casp3↓,
Casp9↑,
P53↑,
p38↑,
MAPK↑,
Cyt‑c↑,
PARP↓,
CHOP↑,
ROS↓,
LDH↑,
GRP78/BiP↑,
ERK↑,
MDA↓,
SOD↑,
GSH↑,
NRF2↑,
VEGF↓,
PDGF↓,
EGF↓,
FGF↓,
TNF-α↓,
TGF-β↓,
VEGFR2↓,
EGFR↓,
FGFR1↓,
mTOR↓,
cMyc↓,
MMPs↓,
LC3B-II↑,
Beclin-1↑,
IL1β↓,
CRP↓,
IL10↓,
COX2↓,
IL6↓,
TLR4↓,
Shh↓,
HER2/EBBR2↓,
NOTCH↓,
DR5↑, quercetin has enhanced DR5 expression in prostate cancer cells
HSP70/HSPA5↓, Quercetin has also suppressed the upsurge of hsp70 expression in prostate cancer cells following heat treatment and enhanced the quantity of subG1 cells
CSCs↓, Quercetin could also suppress cancer stem cell attributes and metastatic aptitude of isolated prostate cancer cells through modulating JNK signaling pathway
angioG↓, Quercetin inhibits angiogenesis-mediated of human prostate cancer cells through negatively modulating angiogenic factors (TGF-β, VEGF, PDGF, EGF, bFGF, Ang-1, Ang-2, MMP-2, and MMP-9)
MMP2↓,
MMP9↓,
IGFBP3↑, Quercetin via increasing the level of IGFBP-3 could induce apoptosis in PC-3 cells
uPA↓, Quercetin through decreasing uPA and uPAR expression and suppressing cell survival protein and Ras/Raf signaling molecules could decrease prostate cancer progression
uPAR↓,
RAS↓,
Raf↓,
TSP-1↑, Quercetin through TSP-1 enhancement could effectively inhibit angiogenesis

2687-

RES,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

NA,

Review,

AD,

NF-kB↓, RES affects NF-kappaB activity and inhibits cytochrome P450 isoenzyme (CYP A1) drug metabolism and cyclooxygenase activity.
P450↓,
COX2↓,
Hif1a↓, RES may inhibit also the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) and thus may have anti-cancer properties
VEGF↓,
*SIRT1↑, RES induces sirtuins, a class of proteins involved in regulation of gene expression. RES is also considered to be a SIRT1-activating compound (STACs).
SIRT1↓, In contrast, decreased levels of SIRT1 and SIRT2 were observed after treatment of BJ cells with concentrations of RES
SIRT2↓,
ChemoSen⇅, However, the effects of RES remain controversial as it has been reported to increase as well as decrease the effects of chemotherapy.
cardioP↑, RES has been shown to protect against doxorubicin-induced cardiotoxicity via restoration of SIRT1
*memory↑, RES has been shown to inhibit memory loss and mood dysfunction which can occur during aging.
*angioG↑, RES supplementation resulted in improved learning in the rats. This has been associated with increased angiogenesis and decreased astrocytic hypertrophy and decreased microglial activation in the hippocampus.
*neuroP↑, RES may have neuroprotective roles in AD and may improve memory function in dementia.
STAT3↓, RES was determined to inhibit STAT3, induce apoptosis, suppress the stemness gene signature and induced differentiation.
CSCs↓,
RadioS↑, synergistically increased radiosensitivity. RES treatment suppressed repair of radiation-induced DNA damage
Nestin↓, RES decreased NESTIN
Nanog↓, RES was determined to suppress the expression of NANOG
TP53↑, RES treatment activated TP53 and p21Cip1.
P21↑,
CXCR4↓, RES downregulated nuclear localization and activity of NF-kappa-B which resulted in decreased expression of MMP9 and C-X-C chemokine receptor type 4 (CXCR4), two proteins associated with metastasis.
*BioAv↓, The pharmacological properties of RES can be enhanced by nanoencapsulation. Normally the solubility and stability of RES is poor.
EMT↓, RES was determined to suppress many gene products associated with EMT such as decreased vimentin and SLUG expression but increased E-cadherin expression.
Vim↓,
Slug↓,
E-cadherin↑,
AMPK↑, RES can induce AMPK which results in inhibition of the drug transporter MDR1 in oxaliplatin-resistant (L-OHP) HCT116/L-OHP CRCs.
MDR1↓,
DNAdam↑, RES induced double strand DNA breaks by interfering with type II topoisomerase.
TOP2↓, The DNA damage was determined to be due to type II topoisomerase poisoning.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt.
Akt↓,
Wnt↓, RES was shown to decrease WNT/beta-catenin pathway activity and the downstream targets c-Myc and MMP-7 in CRC cells.
β-catenin/ZEB1↓,
cMyc↓,
MMP7↓,
MALAT1↓, RES also decreased the expression of long non-coding metastasis associated lung adenocarcinoma transcript 1 (RNA-MALAT1) in the LoVo and HCT116 CRC cells.
TCF↓, Treatment of CRC cells with RES resulted in decreased expression of transcription factor 4 (TCF4), which is a critical effector molecule of the WNT/beta-catenin pathway.
ALDH↓, RES was determined to downregulate ALDH1 and CD44 in HNC-TICs in a dose-dependent fashion.
CD44↓,
Shh↓, RES has been determined to decrease IL-6-induced Sonic hedgehog homolog (SHH) signaling in AML.
IL6↓, RES has been shown to inhibit the secretion of IL-6 and VEGF from A549 lung cancer cells
VEGF↓,
eff↑, Combined RES and MET treatment resulted in a synergistic response in terms of decreased TP53, gammaH2AX and P-Chk2 expression. Thus, the combination of RES and MET might suppress some of the aging effects elicited by UVC-induced DNA damage
HK2↓, RES treatment resulted in a decrease in HK2 and increased mitochondrial-induced apoptosis.
ROS↑, RES was determined to shut off the metabolic shift and increase ROS levels and depolarized mitochondrial membranes.
MMP↓,

4657-

RES,

Resveratrol, cancer and cancer stem cells: A review on past to future

Review,

Var,

CSCs↓, RSV is reported to regulate all the major CSC signaling pathways, but exact mechanisms of its interactions are not clearly understood
CD133↓, CD133(+) cells ↓
Shh↓, Sonic hedgehog (Shh) ↓
Twist↓, GBM Stem cell marker expression: Twist ↓, Snail↓, Slug ↓, MMP-2 ↓, MMP-9 ↓, Smad ↓
Snail↓,
MMP2↓,
MMP9↓,
Smad1↓,
CD44↓, CSC marker proteins: CD44, CD133, ALDH1A1, Oct-4, Nanog ↓
ALDH1A1↓,
OCT4↓,
Nanog↓,
STAT3↓, STAT3 ↓
survivin↓, Survivin, cyclin D1, Cox-2 and c-Myc ↓
cycD1/CCND1↓,
COX2↓,
cMyc↓,

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↓,

5003-

Sal,

Salinomycin, as an autophagy modulator-- a new avenue to anticancer: a review

Review,

Var,

CSCs↓, Since Salinomycin (Sal) emerged its ability to target breast cancer stem cells in 2009, numerous experiments have been carried out to test Sal’s anticancer effects
TumAuto↑, dual role of Sal involving in autophagy may account for its unique anticancer effects
selectivity↑, the mechanism by which Sal brings about cancer cell death while non-malignant cells are exempted from the lethal effects remaining poorly understood.
DNAdam↑, Death receptor - mediated cell death [14], increased DNA damage and cell cycle arrest [22, 23], p-glycoprotein inhibition [24, 25] have been reported to involve the predominant anticancer effects of Sal.
TumCCA↑,
P-gp↓,
Wnt↓, Further studies have demonstrated that Sal suppresses Wnt/β-catenin signaling pathway conferring CSCs resistance to radiation [26, 27] and to chemotherapeutical agents
β-catenin/ZEB1↓,
RadioS↑,
ChemoSen↑,
Shh↓, other studies have showed that Sal blocks the Hedgehog (Hh) pathway, which plays a crucial role in the stemness maintenance of CSCs
eff↓, In addition, pretreatment with NAC, a general ROS scavenger, inhibits Sal-induced autophagy by suppressing ROS production
ROS↑, Sal can lead to the formation of ROS eliciting JNK activation a
AMPK↑, Sal induces a profound AMPK activation.
JNK↑,
ER Stress↑, Sal upregulates ER stress-related proteins such as phospho-EIF2A, ATF4, DDIT3 in a time- and dose- dependent manner in human NSCLC cells.

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.

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↑,

113-

TQ,

Selective Targeting of the Hedgehog Signaling Pathway by PBM Nanoparticles in Docetaxel-Resistant Prostate Cancer

vitro+vivo,

Pca,

C4-2B

 139 uM

 C4-2B-R

HH↓,
Shh↓,
Gli1↓,
eff↑, Furthermore, PEG modification on NP surfaces affects their stability and maximizes the blood circulation half-life [ 31].
TumCP↓, In the present study, we assessed the inhibitory effect of TQ on the Hh pathway, which can, in turn, reduce the proliferation and the chemoresistance of cancer cells

115-

VitD3,

Vitamin D3 Inhibits Hedgehog Signaling and Proliferation in Murine Basal Cell Carcinomas

in-vivo,

RCC,

in-vivo,

BCC,

HH↓,
GLI2↓,
Shh↓,
Gli1↓, topical vitamin D3 treatment of existing murine BCC tumors significantly decreases Gli1 and Ki67 staining.
Ki-67↓,
TumCP↓, Vitamin D3 inhibits proliferation of BCC cell lines

Showing Research Papers: 1 to 27 of 27

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 27

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, Catalase↑, 1, GSH↑, 2, HO-1↑, 1, NRF2↓, 1, NRF2↑, 1, ROS↓, 2,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, NADPH↓, 1, SIRT1↑, 1,

Cell Death ⓘ

Casp3↓, 1,

Migration ⓘ

p‑Rac1↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↑, 1,

Barriers & Transport ⓘ

P-gp↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IKKα↑, 1, IL10↓, 1, IL6↓, 1, Inflam↓, 3, NF-kB↓, 1, PGE2↓, 1, TNF-α↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, BioAv↑, 1,

Clinical Biomarkers ⓘ

ALAT↓, 1, ALP↓, 1, AST↓, 1, IL6↓, 1,

Functional Outcomes ⓘ

cardioP↑, 2, chemoPv↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 3, RenoP↑, 1, toxicity↓, 1, toxicity∅, 1,
Total Targets: 36

Scientific Paper Hit Count for: Shh, sonic hedgehog

6 Curcumin
5 Sulforaphane (mainly Broccoli)
3 Resveratrol
2 Baicalein
2 Ellagic acid
2 Quercetin
1 EGCG (Epigallocatechin Gallate)
1 Germacranolide
1 Graviola
1 Honokiol
1 salinomycin
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#:282  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

Shh 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 ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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