TRAILR Cancer Research Results

TRAILR, tumor necrosis factor-related apoptosis-inducing ligand receptor: Click to Expand ⟱
Source:
Type:
TRAILR refers to TRAIL receptors, which are part of the signaling pathway activated by TNF-related apoptosis-inducing ligand (TRAIL). There are several TRAIL receptors, primarily classified into two categories: death receptors and decoy receptors.
Types of TRAIL Receptors
Death Receptors:
TRAIL-R1 (also known as DR4): This receptor can initiate apoptosis when bound by TRAIL. It contains a death domain that activates downstream signaling pathways leading to cell death.
TRAIL-R2 (also known as DR5): Similar to TRAIL-R1, TRAIL-R2 can also trigger apoptosis upon TRAIL binding. It is often considered more potent in inducing apoptosis compared to TRAIL-R1.
Decoy Receptors:
TRAIL-R3 (also known as DcR1): This receptor does not contain a death domain and cannot initiate apoptosis. Instead, it acts as a decoy, binding TRAIL and preventing it from activating the death receptors.
TRAIL-R4 (also known as DcR2): Like TRAIL-R3, TRAIL-R4 also lacks a death domain and serves as a decoy receptor, inhibiting TRAIL-induced apoptosis.
Scientific Papers found: Click to Expand⟱
170- CUR,    Curcumin sensitizes TRAIL-resistant xenografts: molecular mechanisms of apoptosis, metastasis and angiogenesis
- vitro+vivo, Pca, PC3
TRAILR↑,
BAX↑,
P21↑,
p27↑,
NF-kB↓,
cycD1/CCND1↓,
VEGF↓,
uPA↓,
MMP2↓,
MMP9↓,
Bcl-2↓,
Bcl-xL↓,

2829- FIS,    Fisetin: An anticancer perspective
- Review, Var, NA
TumCP↓, Being a potent anticancer agent, fisetin has been used to inhibit stages in the cancer cells (proliferation, invasion), prevent cell cycle progression, inhibit cell growth, induce apoptosis, cause polymerase (PARP) cleavage
TumCI↓,
TumCCA↑,
TumCG↓,
Apoptosis↑,
cl‑PARP↑,
PKCδ↓, fisetin also suppresses the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways, reduces the NF‐κB activation, and down‐regulates the level of the oncoprotein securin
ROS↓,
ERK↓,
NF-kB↓,
survivin↓,
ROS↑, In human multiple myeloma U266 cells, fisetin stimulated the production of free radical species that led to apoptosis
PI3K↓, Multiple studies also authenticated the anticancer role of fisetin through various signaling pathways such as blocking of mammalian target of rapamycin (PI3K/Akt/mTOR)
Akt↓,
mTOR↓,
MAPK↓, phosphatidylinositol‐3‐kinase/protein kinase B, mitogen‐activated protein kinases (MAPK)‐dependent nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB), and p38, respectively,
p38↓,
HER2/EBBR2↓, (HER2)/neu‐overexpressing breast cancer cell lines. Fisetin caused induction through inactivating the receptor, inducing the degradation of the proteasomes, reducing its half‐life
EMT↓, In addition, mutation of epithelial‐to‐mesenchymal transition (EMT)
PTEN↑, up‐regulation of expression of PTEN mRNA and protein were reported after fisetin treatment
HO-1↑, In breast cancer cells (4T1 and JC cells), fisetin increased HO‐1 mRNA and protein expressions, elevated Nrf2 expression
NRF2↑,
MMP2↓, fisetin reduced MMP‐2 and MMP‐9 enzyme activity and gene expression for both mRNA levels and protein
MMP9↓,
MMP↓, fisetin treatment further led to permeabilization of mitochondrial membrane, activation of caspase‐8 and caspase‐9, as well as the cleavage of poly(ADP‐ribose) polymerase 1
Casp8↑,
Casp9↑,
TRAILR↑, enhanced the levels of TRAIL‐R1
Cyt‑c↑, mitochondrial releasing of cytochrome c into cytosol, up‐regulation and down‐regulation of X‐linked inhibitor of apoptosis protein
XIAP↓,
P53↑, fisetin also enhanced the protein p53 levels
CDK2↓, lowered cell number, the activities of CDK‐2,4)
CDK4↓,
CDC25↓, it also decreased cell division cycle protein levels (CDC)2 and CDC25C, and CDC2 activity (Lu et al., 2005)
CDC2↓,
VEGF↓, down‐regulating the expressions of p‐ERK1/2, vascular endothelial growth factor receptor 1(VEGFR1), p38, and pJNK, respectively
DNAdam↑, Fisetin (80 microM) showed dose‐dependently caused DNA fragmentation, induced cellular swelling and apoptotic death, and showed characteristics of apoptosis.
TET1↓, lowered the TET1 expression levels
CHOP↑, caused up‐regulation of (C/EBP) homologous protein (CHOP) expression and reactive oxygen species production,
CD44↓, down‐regulation of CD44 and CD133 markers
CD133↓,
uPA↓, down‐regulation of levels of matrix metalloproteinase‐2 (MMP‐2), urokinase‐type plasminogen activator (uPA),
CSCs↓, Being a potent anticancer agent, fisetin administration in in vitro and in vivo studies in kidney renal stem cells (HuRCSCs) effectively inhibited cancer cell stages such as proliferation,

1644- HCAs,  PBG,    Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) sensitizes LNCaP prostate cancer cells to TRAIL-induced apoptosis
- in-vitro, Pca, LNCaP
NF-kB↓,
TRAILR↑, Artepillin C increased the expression of TRAIL-R2 and decreased the activity of NF-κB
Casp8↑, Co-treatment with TRAIL and artepillin C induced the significant activation of caspase-8 and caspase-3, as well as the disruption of ΔΨm
Casp3↑,
MMP↓,
Dose?, co-treatment of LNCaP cells with 100 ng/ml TRAIL and 50–100 μM artepillin C for 24 h the cytotoxicity ranged from 59.3±1.6 to 66.3±2.3%.

4968- PSO,    Psoralidin: emerging biological activities of therapeutic benefits and its potential utility in cervical cancer
- in-vitro, Cerv, NA
*Inflam↓, showing anti-inflammatory, anti-oxidant, estrogenic, neuroprotective, anti-diabetic, anti-depressant, antimicrobial, and anti-tumor activities substantiate its promising biological effects.
*antiOx↑,
*neuroP↑,
*AntiDiabetic↑,
*Bacteria↓,
AntiTum↑,
CSCs↓, Its capacity to effectively target cancer stem cells (CSCs) in general adds to its therapeutic potential.
ROS↑, Psoralidin carries out its anti-cancer activity by inducing oxidative stress, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
ChemoSen↑, This unique characteristic suggests its potential to be used as an adjunct molecule in combination with existing treatment to enhance the efficacy of chemo/radiotherapy for treating CaCx.
RadioS↑,
BioAv↓, low bioavailability and intestinal efflux limit the use of psoralidin in clinical applications
*cardioP↑, Psoralidin demonstrated cardioprotective effects.
*ROS↓, Furthermore, psoralidin administration resulted in a decrease in ROS levels and lactate dehydrogenase (LDH) release, indicating reduced oxidative stress and cellular damage in the heart.
*LDH↓,
TumCP↓, LNCaP Induction of apoptosis ↓Cell proliferation ↑TRAIL
TRAIL⇅,
TumCMig↓, PC-3, PzHPV-7, C4-2B 5–20 µM ↓Cell proliferation, ↓Migration, Invasion ROS generation
EMT↓, RWPE-1, xenograft mice 4 µM ↓Cell proliferation, Induction of apoptosis, Autophagy induction, EMT Inhibition ↓NF-кB signaling
NF-kB↓,
P53↑, HepG2 64 µM Induction of apoptosis ↑p53
Casp3↑, figure 4
NOTCH↓,
CSCs↓, Anti-CSC activity
angioG↓, Anti-angiogenesis
VEGF↓, it inhibited angiogenesis by downregulating the expression of pro-angiogenic molecules VEGF, Ki67, and CD31
Ki-67↓,
CD31↓,
TRAILR↑, psoralidin treatment induced the activation of death receptors 1 (DR 1) and DR 2 after 48 h of treatment
MMP↓, Psoralidin significantly increased the loss of ΔΨm, affecting a large percentage of cancer cells (58.38% ± 1.41%) and causing a major disruption of the mitochondrial membrane potential.
BioAv↓, hydrophobic nature, inadequate pharmacokinetic profile of psoralidin, and intestinal efflux, which hampers its clinical application
BioAv↑, bioavailability of psoralidin significantly improved with a value of 339% w.r.t to reference through its nanoencapsulation (NCs) using chitosan and Eudragit S100

48- QC,    Quercetin Potentiates Apoptosis by Inhibiting Nuclear Factor-kappaB Signaling in H460 Lung Cancer Cells
- in-vitro, NSCLC, H460
TRAILR↑, quercetin increased the expression of genes associated with death receptor signaling tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAILR), caspase-10, interleukin (IL) 1R DNA fragmentation faotor 45 (DFF45), tumor necrosis fact
Casp10↑,
DFF45↑,
TNFR 1↑,
Fas↑,
NF-kB↓, Quercetin Potentiates Apoptosis by Inhibiting Nuclear Factor-kappaB Signaling in H460 Lung Cancer Cells
IKKα↓,

923- QC,    Quercetin as an innovative therapeutic tool for cancer chemoprevention: Molecular mechanisms and implications in human health
- Review, Var, NA
ROS↑, decided by the availability of intracellular reduced glutathione (GSH),
GSH↓, extended exposure with high concentration of quercetin causes a substantial decline in GSH levels
Ca+2↝,
MMP↓,
Casp3↑, activation of caspase-3, -8, and -9
Casp8↑,
Casp9↑,
other↓, when p53 is inhibited, cancer cells become vulnerable to quercetin-induced apoptosis
*ROS↓, Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors.
*NRF2↑, Moreover, the therapeutic efficacy of QC has also been defined in rat models through the activation of Nrf-2/HO-1 against high glucose-induced damage
HO-1↑,
TumCCA↑, QC increases cell cycle arrest via regulating p21WAF1, cyclin B, and p27KIP1
Inflam↓, QC-mediated anti-inflammatory and anti-apoptotic properties play a key role in cancer prevention by modulating the TLR-2 (toll-like receptor-2) and JAK-2/STAT-3 pathways and significantly inhibit STAT-3 tyrosine phosphorylation within inflammatory ce
STAT3↓,
DR5↑, several studies showed that QC upregulated the death receptor (DR)
P450↓, it hinders the activity of cytochrome P450 (CYP) enzymes in hepatocytes
MMPs↓, QC has also been shown to suppress metastatic protein expression such as MMPs (matrix metalloproteases)
IFN-γ↓, QC is its ability to inhibit inflammatory mediators including IFN-γ, IL-6, COX-2, IL-8, iNOS, TNF-α,
IL6↓,
COX2↓,
IL8↓,
iNOS↓,
TNF-α↓,
cl‑PARP↑, Induced caspase-8, caspase-9, and caspase-3 activation, PARP cleavage, mitochondrial membrane depolarization,
Apoptosis↑, increased apoptosis and p53 expression
P53↑,
Sp1/3/4↓, HT-29 colon cancer cells: decreased the expression of Sp1, Sp3, Sp4 mrna, and survivin,
survivin↓,
TRAILR↑, H460 Increased the expression of TRAILR, caspase-10, DFF45, TNFR 1, FAS, and decreased the expression of NF-κb, ikkα
Casp10↑,
DFF45↑,
TNFR 1↑,
Fas↑,
NF-kB↓,
IKKα↓,
cycD1/CCND1↓, SKOV3 Reduction in cyclin D1 level
Bcl-2↓, MCF-7, HCC1937, SK-Br3, 4T1, MDA-MB-231 Decreased Bcl-2 expression, increasedBax expression, inhibition of PI3K-Akt pathway
BAX↑,
PI3K↓,
Akt↓,
E-cadherin↓, MDA-MB-231 Induced the expression of E-cadherin and downregulated vimentin levels, modulation of β-catenin target genes such as cyclin D1 and c-Myc
Vim↓,
β-catenin/ZEB1↓,
cMyc↓,
EMT↓, MCF-7 Suppressed the epithelial–mesenchymal transition process, upregulated E-cadherin expression, downregulated vimentin and MMP-2 expression, decreased Notch1 expression
MMP2↓,
NOTCH1↓,
MMP7↓, PANC-1, PATU-8988 Decreased the secretion of MMP and MMP7, blocked the STAT3 signaling pathway
angioG↓, PC-3, HUVECs Reduced angiogenesis, increased TSP-1 protein and mrna expression
TSP-1↑,
CSCs↓, PC-3 and LNCaP cells Activated capase-3/7 and inhibit the expression of Bcl-2, surviving and XIAP in CSCs.
XIAP↓,
Snail↓, inhibiting the expression of vimentin, slug, snail and nuclear β-catenin, and the activity of LEF-1/TCF responsive reporter
Slug↓,
LEF1↓,
P-gp↓, MCF-7 and MCF-7/dox cell lines Downregulation of P-gp expression
EGFR↓, MCF-7 and MDA-MB-231 cells Suppressed EGFR signaling and inhibited PI3K/Akt/mTOR/GSK-3β
GSK‐3β↓,
mTOR↓,
RAGE↓, IA Paca-2, BxPC3, AsPC-1, HPAC and PANC1 Silencing RAGE expression
HSP27↓, Breast cancer In vivo NOD/SCID mice Inhibited the overexpression of Hsp27
VEGF↓, QC significantly reversed an elevation in profibrotic markers (VEGF, IL-6, TGF, COL-1, and COL-3)
TGF-β↓,
COL1↓,
COL3A1↓,


Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSH↓, 1,   HO-1↑, 2,   NRF2↑, 1,   ROS↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   MMP↓, 4,   XIAP↓, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 3,   BAX↑, 2,   Bcl-2↓, 2,   Bcl-xL↓, 1,   Casp10↑, 2,   Casp3↑, 3,   Casp8↑, 3,   Casp9↑, 2,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 2,   iNOS↓, 1,   MAPK↓, 1,   p27↑, 1,   p38↓, 1,   survivin↓, 2,   TNFR 1↑, 2,   TRAIL⇅, 1,   TRAILR↑, 6,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   HSP27↓, 1,  

Autophagy & Lysosomes ⓘ

TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DFF45↑, 2,   DNAdam↑, 1,   P53↑, 3,   cl‑PARP↑, 2,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycD1/CCND1↓, 2,   P21↑, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   CSCs↓, 4,   EMT↓, 3,   ERK↓, 1,   GSK‐3β↓, 1,   mTOR↓, 2,   NOTCH↓, 1,   NOTCH1↓, 1,   PI3K↓, 2,   PTEN↑, 1,   STAT3↓, 1,   TumCG↓, 1,  

Migration ⓘ

Ca+2↝, 1,   CD31↓, 1,   COL1↓, 1,   COL3A1↓, 1,   E-cadherin↓, 1,   Ki-67↓, 1,   LEF1↓, 1,   MMP2↓, 3,   MMP7↓, 1,   MMP9↓, 2,   MMPs↓, 1,   PKCδ↓, 1,   RAGE↓, 1,   Slug↓, 1,   Snail↓, 1,   TET1↓, 1,   TGF-β↓, 1,   TSP-1↑, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   uPA↓, 2,   Vim↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   EGFR↓, 1,   VEGF↓, 4,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IFN-γ↓, 1,   IKKα↓, 2,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 1,   NF-kB↓, 6,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   ChemoSen↑, 1,   Dose?, 1,   P450↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,   Ki-67↓, 1,   RAGE↓, 1,  

Functional Outcomes ⓘ

AntiTum↑, 1,  
Total Targets: 106

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   NRF2↑, 1,   ROS↓, 2,  

Core Metabolism/Glycolysis ⓘ

LDH↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  

Clinical Biomarkers ⓘ

LDH↓, 1,  

Functional Outcomes ⓘ

AntiDiabetic↑, 1,   cardioP↑, 1,   neuroP↑, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 10

Scientific Paper Hit Count for: TRAILR, tumor necrosis factor-related apoptosis-inducing ligand receptor
2 Quercetin
1 Curcumin
1 Fisetin
1 Hydroxycinnamic-acid
1 Propolis -bee glue
1 Psoralidin
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

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