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↓,

18-

CBC/D,

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

vitro+vivo,

MB,

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

17-

CBC/D,

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

in-vivo,

CRC,

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

16-

CP,

RES,

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

in-vitro,

GC,

SGC-7901

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

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.

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

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↓,

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↓,

3379-

QC,

The Effect of Quercetin Nanosuspension on Prostate Cancer Cell Line LNCaP via Hedgehog Signaling Pathway

in-vitro,

Pca,

LNCaP

tumCV↓, The cell viability gradually decreased with increased concentration of quercetin nanoparticles.
HH↓, To sum up, nanoparticles of quercetin improved the inhibitory role in progression of PCa on cell line LNCaP via Hh signaling pathway. targeted inhibition of the Hh pathway could also be an efficient way to stop PCa progression.

101-

RES,

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

in-vitro,

GC,

SGC-7901

 10 uM

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

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

4667-

RES,

CUR,

SFN,

Physiological modulation of cancer stem cells by natural compounds: Insights from preclinical models

Review,

Var,

CSCs↓, phytochemicals such as resveratrol, curcumin, sulforaphane, and others suppress CSC-associated pathways as well as sensitize CSCs to chemotherapy and radiotherapy
ChemoSen↑,
RadioS↑,
ALDH↓, deplete ALDH+ or CD44+ CSC pools, which ultimately decrease tumor initiation and recurrence.
CD44↓,
Wnt↓, graphical abstract
β-catenin/ZEB1↓,
NOTCH↓,
HH↓,
NF-kB↓,

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↓,

1747-

RosA,

Molecular Pathways of Rosmarinic Acid Anticancer Activity in Triple-Negative Breast Cancer Cells: A Literature Review

Review,

BC,

MDA-MB-231

Review,

BC,

MDA-MB-468

TumCCA↑, Rosmarinic Acid arrests the G0/G1 phase in MDA-MB-231 cells and the S-phase in MDA-MB-468 cells following apoptosis (interruption of the G2/M process).
TNF-α↑, Rosmarinic Acid enhanced the expression of TNF (tumor necrosis factor), GADD45A (growth arrest and DNA damage-inducible 45 alpha), and the proapoptotic BNIP3
GADD45A↑,
BNIP3↑,
survivin↓, IRC5 (Survivin) inhibition appears to be the most important effect of Rosmarinic Acid on MDA-MB-468 cells
Bcl-2↓, Bcl-2 gene is downregulated while the Bax gene expression is increased in the presence of Rosmarinic Acid
BAX↑,
HH↓, The experiments showed that Rosmarinic Acid inhibited Hh signaling genes’ expression in BCSCs.
eff↑, rosemary extract with Rosmarinic Acid and carnosic acid as primary ingredients inhibited cancer cell viability in the ER+, HER2+, and TNBC subtypes (MDA-MB-231 and MDA-MB-468 cells)
ChemoSen↑, The inhibition of NF-κB increases chemotherapy and radiation results
RadioS↑,
TumCP↓, In vitro experiments in MDA-MB-231 cancer cells treated with Rosmarinic Acid have shown that proliferation and migration were significantly attenuated, and eventually, cells were led to apoptosis
TumCMig↓,
Apoptosis↑,
RenoP↑, Rosmarinic Acid decreased the hepatic and renal toxicity induced by methotrexate, as well as the cardiotoxicity of doxorubicin
CardioT↓,

1744-

RosA,

Therapeutic Applications of Rosmarinic Acid in Cancer-Chemotherapy-Associated Resistance and Toxicity

Review,

Var,

chemoR↓, Recently, several studies have shown that RA is able to reverse cancer resistance to first-line chemotherapeutics
ChemoSideEff↓, as well as play a protective role against toxicity induced by chemotherapy and radiotherapy
RadioS↑, RA decreased radiation-induced ROS with RA by 21% compared to control
ROS↓, mainly due to its scavenger capacity
ChemoSen↑, recent years, evidence has emerged demonstrating the ability of RA to act as a chemosensitizer
BioAv↑, bioavailability of RA have been studied in animal models, revealing rapid absorption in the stomach and intestine
Half-Life↝, Urine was the primary route of RA excretion, with 83% of the total metabolites excreted during the period from 8 to 18 h after RA administration
antiOx↑, RA, well known for its antioxidant properties,
ROS↑, has recently been identified as a potential pro-oxidant in the presence of superoxide anions.
Fenton↑, Studies indicate that RA can facilitate the reduction of Cu (II) to Cu (I) and Fe (III) to Fe (II) leading to Fenton-type reactions that generate reactive hydroxyl radicals (HO˙)
DNAdam↑, These radicals are implicated in DNA damage and induction of apoptosis in cancer cells
Apoptosis↑,
CSCs↓, RA has demonstrated potential in controlling breast cancer stem cells (CSCs)
HH↓, RA inhibits stem-like breast cancer cells by targeting the hedgehog signaling pathway and modulating the Bcl-2/Bax ratio at concentrations of 270 and 810 μM
Bax:Bcl2↑,
MDR1↓, It has been observed to downregulate P-glycoprotein (P-gp) expression and decrease MDR1 gene transcription, thereby reversing MDR.
P-gp↓,
eff↑, RA has been reported to modulate the ADAM17/EGFR/AKT/GSK3β signaling axis in A375 melanoma cells, potentially enhancing synergy with cisplatin
eff↑, RA has demonstrated effectiveness in enhancing chemosensitivity to 5-FU, a commonly used chemotherapy agent for gastrointestinal cancers.
FOXO4↑, By upregulating FOXO4 expression, RA restored the sensitivity of cells to 5-FU
*eff↑, RA has been shown to reduce DOX-induced apoptosis in H9c2 cardiac muscle cells, and reduce intracellular ROS generation through downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), as well as to restore the
*ROS↓,
*JNK↓,
*ERK↓,
*GSH↑, RA has also shown an antioxidant role, which is evidenced by the ability and recovery of levels of glutathione (GSH), hydrogen peroxide (H2O2), and superoxide radicals (O2·), reducing the expression of malondialdehyde
*H2O2↑,
*MDA↓,
*SOD↑, regulating the expression of antioxidant enzymes such as superoxide dismutase (SOD), as well as upregulating catalase heme oxygenase-1, resulting in significantly improved viability
*HO-1↑,
*CardioT↓, The cardioprotective effect of RA
selectivity↑, RA blocked caspases 3 and 9 activation, cytochrome c release, and ROS generation induced by cisplatin in HEI-OC1(normal)cells

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↓,

109-

SIL,

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

vitro+vivo,

RCC,

769-P

in-vitro,

RCC,

786-O

in-vitro,

RCC,

ACHN

in-vitro,

RCC,

OS-RC-2

 (50-200 uM) 200mg/kg vivo

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

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%,

112-

SuD,

Inhibition of Gli/hedgehog signaling in prostate cancer cells by “cancer bush” Sutherlandia frutescens extract

in-vitro,

Pca,

PC3

 167 ug/mL

in-vitro,

Pca,

LNCaP

HH↓, S. frutescens extract (SLE) suppressed the Gli/Hh signaling in Shh Light II cell line
Gli1↓, S. frutescens extract also inhibited Gli/Hh signaling activity by reducing Gli1 and PTCH1 gene expression in TRAMP-C2 and PC3 cells
PTCH1↓,
TumCG↓, S. frutescens extract (SLE) inhibited the growth of human and mouse prostate cancer cell lines
chemoPv↑, Furthermore, major triterpenoids of S. frutescens are structurally related to cycloartane-type tritepenoids which have cancer chemopreventive activity (
eff↑, S. frutescens extract is potentially safe and effective for the prevention and treatment of advanced prostate cancers with upregulated Gli/Hh signaling activity.

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

Showing Research Papers: 1 to 50 of 51
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 51

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 3, Catalase↑, 1, GPx↑, 1, GSH↑, 1, H2O2↓, 1, H2O2↑, 1, HO-1↑, 1, MDA↓, 1, ROS↓, 2, SOD↑, 2,

Cell Death ⓘ

JNK↓, 1,

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,

Drug Metabolism & Resistance ⓘ

eff↑, 1,

Functional Outcomes ⓘ

CardioT↓, 1, chemoPv↑, 1, toxicity↓, 1,
Total Targets: 18

Scientific Paper Hit Count for: HH, Hedgehog signaling

8 Curcumin
6 Resveratrol
6 EGCG (Epigallocatechin Gallate)
3 Apigenin (mainly Parsley)
3 Genistein (soy isoflavone)
3 itraconazole
3 Sulforaphane (mainly Broccoli)
2 Quercetin
2 Cynanbungeigenin C (CBC) and D (CBD)
2 Glabrescione B
2 Rosmarinic acid
1 Acoschimperoside P, 2’-acetate
1 Andrographis
1 Artemisinin
1 Baicalein
1 Berberine
1 Betulinic acid
1 Cyclopamine
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 ⓘ

Cell Death ⓘ

Proliferation, Differentiation & Cell State ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Functional Outcomes ⓘ

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