Smo Cancer Research Results

Smo, G-protein-coupled receptor-like 7-pass transmembrane protein Smoothened: Click to Expand ⟱

Source: CGL-Driver Genes

Type: HH Oncogene

Smoothened homolog (Drosophila)
SMO, or Smoothened, is a protein that plays a crucial role in the Hedgehog signaling pathway, which is important for cell growth, differentiation, and tissue patterning during embryonic development. Inhibitors of SMO, such as vismodegib and sonidegib, have been developed as targeted therapies for cancers associated with aberrant Hedgehog signaling.
SMO (Smoothened):
- A G protein-coupled receptor (GPCR)-like protein that is a critical component of the Hedgehog (Hh) signaling pathway.
- Functions in transmitting the Hedgehog signal from the cell surface to intracellular effectors, culminating in changes in gene expression.
Aberrant Activation of the Hedgehog Pathway:
- In many cancers, mutations or dysregulations in pathway components lead to ligand-independent or ligand-dependent activation of SMO.
- This inappropriate activation can result in enhanced cell proliferation, survival, and stem cell-like
Several cancers exhibit overexpression of SMO or activating mutations leading to Hedgehog pathway activation.
Smoothened (SMO) is a critical mediator of the Hedgehog signaling pathway, with aberrant activation contributing to tumor growth, progression, and resistance to therapy. High expression or activating mutations in SMO are linked with a poor prognosis in certain cancer types, particularly in cancers that are dependent on Hedgehog pathway signaling such as basal cell carcinoma and medulloblastoma. By targeting SMO with specific inhibitors, researchers and clinicians are addressing one of the key drivers of tumorigenesis in these settings.

Scientific Papers found: Click to Expand⟱

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↓,

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

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

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.

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↓,

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

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.

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

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↑,

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)

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↑,

102-

RES,

Effect of resveratrol on proliferation and apoptosis of human pancreatic cancer MIA PaCa-2 cells may involve inhibition of the Hedgehog signaling pathway

in-vitro,

PC,

MIA PaCa-2

HH↓, the levels of Ihh, Ptch and Smo were decreased by Res treatment
PTCH1↓,
Smo↓,
HH↓, Ihh
EMT↓,
PI3K/Akt↓, thru PI-3K/Akt/NF-κB↓
NF-kB↓,
TumCP↓, Res can inhibit the cell proliferative ability in a time- and dose-dependent manner.
Apoptosis↑, Res further induced apoptosis of MIA PaCa-2 cells in a dose-dependent manner.
ChemoSen↑, The apoptotic rate was significantly increased in cells treated with 5-Fu and Res, and the number of apoptotic cells increased with the increasing concentrations of Res

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↓,

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↑,

107-

SS,

Saikosaponin B1 and Saikosaponin D inhibit tumor growth in medulloblastoma allograft mice via inhibiting the Hedgehog signaling pathway

vitro+vivo,

MB,

LS174T

 241.8 nM

 SSB1

HH↓, SSB1 and SSD inhibit Hedgehog signaling pathway activity in vitro
Smo↓, SSB1 and SSD potentially inhibit the Hedgehog pathway by targeting SMO
Gli↓, luciferase
Gli1↓,
PTCH1↓,
TumCG↓, Inhibition of cell proliferation and tumor growth tumor growth inhibition ratios were approximately 50% and 70%,

Showing Research Papers: 1 to 25 of 25

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 25

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, ROS↓, 1, SOD↑, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,

Functional Outcomes ⓘ

cardioP↑, 1, chemoPv↑, 1, hepatoP↑, 1, neuroP↑, 1, toxicity↓, 1,
Total Targets: 14

Scientific Paper Hit Count for: Smo, G-protein-coupled receptor-like 7-pass transmembrane protein Smoothened

6 Sulforaphane (mainly Broccoli)
4 EGCG (Epigallocatechin Gallate)
3 Resveratrol
2 Curcumin
1 Andrographis
1 Baicalein
1 Berberine
1 Carvacrol
1 Thymol-Thymus vulgaris
1 Genistein (soy isoflavone)
1 Graviola
1 Inoscavin A
1 itraconazole
1 salinomycin
1 Saikosaponin B1 and D

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:287  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

Smo Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

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 ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

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