Purity: > 98%
iCRT3(cas 901751-47-1) is an inhibitor of the Wnt/wingless signaling pathway. iCRT3 efficiently block Wnt/β-catenin-induced target genes and phenotypes in various mammalian and cancer cell lines. Importantly, these Wnt inhibitors are specifically cytotoxic to human colon tumor biopsy cultures as well as colon cancer cell lines that exhibit deregulated Wnt signaling.
1. Mol Cells. 2018 Sep 30;41(9):830-841. doi: 10.14348/molcells.2018.0181. Epub 2018
MicroRNA-766-3p Inhibits Tumour Progression by Targeting Wnt3a in Hepatocellular
You Y(1), Que K(1), Zhou Y(1), Zhang Z(1), Zhao X(1), Gong J(1), Liu Z(1).
(1)Department of Hepatobiliary Surgery, the Second Affiliated Hospital of
Chongqing Medical University, Chongqing 400010, China.
Recent studies have indicated that microRNAs (miRNAs) play an important role in
hepatocellular carcinoma (HCC) progression. In this study, we showed that
miR-766-3p was decreased in approximately 72% of HCC tissues and cell lines, and
its low expression level was significantly correlated with tumour size, TNM
stage, metastasis, and poor prognosis in HCC. Ectopic miR-766-3p expression
inhibited HCC cell proliferation, colony formation, migration and invasion. In
addition, we showed that miR-766-3p repressed Wnt3a expression. A luciferase
reporter assay revealed that Wnt3a was a direct target of miR-766-3p, and an
inverse correlation between miR-766-3p and Wnt3a expression was observed.
Moreover, Wnt3a up-regulation reversed the effects of miR-766-3p on HCC
progression. In addition, our study showed that miR-766-3p up-regulation
decreased the nuclear β-catenin level and expression of Wnt targets (TCF1 and
Survivin) and reduced the level of MAP protein regulator of cytokinesis 1 (PRC1).
However, these effects of miR-766-3p were reversed by Wnt3a up-regulation. In
addition, PRC1 up-regulation increased the nuclear β-catenin level and protein
expression of TCF1 and Survivin. iCRT3, which disrupts the β-catenin-TCF4
interaction, repressed the TCF1, Survivin and PRC1 protein levels. Taken
together, our results suggest that miR-766-3p down-regulation promotes HCC cell
progression, probably by targeting the Wnt3a/PRC1 pathway, and miR-766-3p may
serve as a potential therapeutic target in HCC.
2. Cell Physiol Biochem. 2017;43(5):2133-2142. doi: 10.1159/000484232. Epub 2017 Oct
A Novel Positive Feedback Loop Between NTSR1 and Wnt/β-Catenin Contributes to
Tumor Growth of Glioblastoma.
Xiao H, Zeng Y, Wang Q, Wei S, Zhu X.
BACKGROUND/AIMS: Neurotensin (NTS), an intestinal hormone, is profoundly
implicated in cancer progression through binding its primary receptor NTSR1. The
conserved Wnt/β-Catenin pathway regulates cell proliferation and differentiation
via activation of the β-catenin/T-cell factor (TCF) complex and subsequent
modulation of a set of target genes. In this study, we aimed to uncover the
potential connection between NTS/NTSR1 signaling and Wnt/β-Catenin pathway.
METHODS: Genetic silencing, pharmacological inhibition and gain-of-function
studies as well as bioinformatic analysis were performed to uncover the link
between NTS/ NTSR1 signaling and Wnt/β-Catenin pathway. Two inhibitors were used
in vivo to evaluate the efficiency of targeting NTS/NTSR1 signaling or
RESULTS: We found that NTS/NTSR1 induced the activation of mitogen-activated
protein kinase (MAPK) and the NF-κB pathway, which further promoted the
expression of Wnt proteins, including Wnt1, Wnt3a and Wnt5a. Meanwhile, the mRNA
and protein expression levels of NTSR1 were increased by the Wnt pathway
activator Wnt3a and decreased by the Wnt inhibitor iCRT3 in glioblastoma cells.
Furthermore, pharmacological inhibition of NTS/NTSR1 or Wnt/β-Catenin signaling
suppressed tumor growth in vitro and in vivo.
CONCLUSION: These results reveal a positive feedback loop between NTS/NTSR1 and
Wnt/β-Catenin signaling in glioblastoma cells that might be important for tumor
development and provide potential therapeutic targets for glioblastoma.
3. Sci Rep. 2017 Aug 23;7(1):9235. doi: 10.1038/s41598-017-08711-6.
Mitigation of sepsis-induced inflammatory responses and organ injury through
targeting Wnt/β-catenin signaling.
Sharma A(1), Yang WL(1)(2), Ochani M(1), Wang P(3)(4).
(1)Center for Immunology and Inflammation, The Feinstein Institute for Medical
Research, Manhasset, NY, 11030, USA.
(2)Department of Surgery, Hofstra Northwell School of Medicine, Manhasset, NY,
(3)Center for Immunology and Inflammation, The Feinstein Institute for Medical
Research, Manhasset, NY, 11030, USA. firstname.lastname@example.org.
(4)Department of Surgery, Hofstra Northwell School of Medicine, Manhasset, NY,
11030, USA. email@example.com.
The Wnt/β-catenin pathway has been involved in regulating inflammation in various
infectious and inflammatory diseases. Sepsis is a life-threatening condition
caused by dysregulated inflammatory response to infection with no effective
therapy available. Recently elevated Wnt/β-catenin signaling has been detected in
sepsis. However, its contribution to sepsis-associated inflammatory response
remains to be explored. In this study, we show that inhibition of Wnt/β-catenin
signaling reduces inflammation and mitigates sepsis-induced organ injury. Using
in vitro LPS-stimulated RAW264.7 macrophages, we demonstrate that a
small-molecule inhibitor of β-catenin responsive transcription, iCRT3,
significantly reduces the LPS-induced Wnt/β-catenin activity and also inhibits
TNF-α production and IκB degradation in a dose-dependent manner. Intraperitoneal
administration of iCRT3 to C57BL/6 mice, subjected to cecal ligation and
puncture-induced sepsis, decreases the plasma levels of proinflammatory cytokines
and organ injury markers in a dose-dependent manner. The histological integrity
of the lungs is improved with iCRT3 treatment, along with reduced lung collagen
deposition and apoptosis. In addition, iCRT3 treatment also decreases the
expression of the cytokines, neutrophil chemoattractants, as well as the MPO
activity in the lungs of septic mice. Based on these findings we conclude that
targeting the Wnt/β-Catenin pathway may provide a potential therapeutic approach
for treatment of sepsis.