Bisindoylmaleimide I enhances osteogenic differentiation

Zhou, Fangfang; Huang, Huizhe; Zhang, Long

doi:10.1007/s13238-012-2027-4

Cited by 7 publications

(4 citation statements)

References 42 publications

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“…Alternatively, the BIS I induced inhibition of PKCδ/GSK3β activity can lead to the degradation of the destruction complex as proved by β-catenin and YAP nuclear accumulation. Inhibition of the GSK3β by BIS I led to osteogenic differentiation and suppression of adipocyte differentiation by β-catenin stabilization [ 42 , 43 ]. More importantly, these data are in agreement with the inhibition of the GSK3β by BIO that led to the activation of YAP/TEAD response [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

The GSK3β inhibitor BIS I reverts YAP-dependent EMT signature in PDAC cell lines by decreasing SMADs expression level

Thongon

Castiglioni²,

Zucal

et al. 2016

Oncotarget

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The Yes-associated protein, YAP, is a transcriptional co-activator, mediating the Epithelial to Mesenchymal Transition program in pancreatic ductal adenocarcinoma (PDAC). With the aim to identify compounds that can specifically modulate YAP functionality in PDAC cell lines, we performed a small scale, drug-based screening experiment using YAP cell localization as the read-out. We identified erlotinib as an inducer of YAP cytoplasmic localization, an inhibitor of the TEA luciferase reporter system and the expression of the bona fide YAP target gene, Connective Tissue Growth Factor CTGF. On the other hand, BIS I, an inhibitor of PKCδ and GSK3β, caused YAP accumulation into the nucleus. Activation of β-catenin reporter and interfering experiments show that inhibition of the PKCδ/GSK3β pathway triggers YAP nuclear accumulation inducing YAP/TEAD transcriptional response. Inhibition of GSK3β by BIS I reduced the expression levels of SMADs protein and reduced YAP contribution to EMT. Notably, BIS I reduced proliferation, migration and clonogenicity of PDAC cells in vitro, phenocopying YAP genetic down-regulation. As shown by chromatin immunoprecipitation experiments and YAP over-expressing rescue experiments, BIS I reverted YAP-dependent EMT program by modulating the expression of the YAP target genes E-cadherin, vimentin, CTGF and of the newly identified target, CD133. In conclusion, we identified two different molecules, erlotinib and BIS I, modulating YAP functionality although via different mechanisms of action, with the second one specifically inhibiting the YAP-dependent EMT program in PDAC cell lines.

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Section: Discussionmentioning

confidence: 99%

The GSK3β inhibitor BIS I reverts YAP-dependent EMT signature in PDAC cell lines by decreasing SMADs expression level

Thongon

Castiglioni²,

Zucal

et al. 2016

Oncotarget

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“…#610153) was purchased from BD Biosciences; ERK(#4695), pERK(#9106), GSK3β(#9832), pSer9 GSK3β(#9323), Akt(#4685), pAkt 473(#4058) and Actin(#4970) were purchased from Cell Signaling Technology, Inc (USA); LPS, LY294002, PD98059 were purchased from Sigma, USA. β-catenin SY, dnLEF-1 and GSK3β S9A and control constructs were previously described (Zhang et al, 2006(Zhang et al, , 2012cZhou et al, 2012aZhou et al, , 2012b.…”

Section: Reagent and Plasmidsmentioning

confidence: 99%

Suppression of GSK3β by ERK mediates lipopolysaccharide induced cell migration in macrophage through β-catenin signaling

et al. 2012

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We investigate the role of β-catenin signaling in the response of macrophage to lipopolysaccharide (LPS) using RAW264.7 cells. LPS rapidly stimulated cytosolic β-catenin accumulation. β-catenin-mediated transcription was showed to be required for LPS induced gene expression and cell migration. Mechanically, ERK activation-primed GSK3β inactivation by Akt was demonstrated to mediate the LPS induced β-catenin accumulation. Overall, our findings suggest that suppression of GSK3β by ERK stimulates β-catenin signaling therefore contributes to LPS induced cell migration in macrophage activation.

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“…It was also discovered as a competitive inhibitor of ATP ( K i = 14 nM) and it efficiently halted PKC-mediated phosphorylation and successfully inhibited collagen-triggered ATP secretion and collagen- and thrombin-induced platelet aggregation. As well as being used as a standard molecular tool to explore the role of PKC in disease, more recently GF109203X has been identified as a potent agonist of β-catenin accumulation in preosteoblast cells, promoting osteoblast differentiation and bone formation (through suppression of GSK-3β kinase) [ 42 , 43 ]. Another new application was identified in 2017 in the inhibition of exosome and microvesicle release to improve the efficiency of cancer treatment [ 44 ].…”

Section: Bioactivity Of Bisindolylmaleimides and Derivativesmentioning

confidence: 99%

Bisindolyl Maleimides and Indolylmaleimide Derivatives—A Review of Their Synthesis and Bioactivity

Cooney,

O’Shea,

Winfield

et al. 2023

Pharmaceuticals

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The evolution of bisindolyl maleimides and indolyl maleimide derivatives and their unique biological activities have stimulated great interest in medicinal chemistry programs. Bisindolylmaleimide (BIM)-type compounds arise from natural sources such as arcyriarubin and are biosynthetically related to indolocarbazoles. BIMs are commonly the immediate synthetic precursors of indolocarbazoles, lacking a central bond between the two aromatic units and making them more flexible and drug-like. Synthetic endeavours within this class of compounds are broad and have led to the development of both remarkably potent and selective protein kinase inhibitors. Clinical BIM examples include ruboxistaurin and enzastaurin, which are highly active inhibitors of protein kinase C-β. While BIMs are widely recognised as protein kinase inhibitors, other modes of activity have been reported, including the inhibition of calcium signalling and antimicrobial activity. Critically, structural differences can be used to exploit new bioactivity and therefore it is imperative to discover new chemical entities to address new targets. BIMs can be highly functionalised or chemically manipulated, which provides the opportunity to generate new derivatives with unique biological profiles. This review will collate new synthetic approaches to BIM-type compounds and their associated bioactivities with a focus on clinical applications.

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Bisindoylmaleimide I enhances osteogenic differentiation

Cited by 7 publications

References 42 publications

The GSK3β inhibitor BIS I reverts YAP-dependent EMT signature in PDAC cell lines by decreasing SMADs expression level

The GSK3β inhibitor BIS I reverts YAP-dependent EMT signature in PDAC cell lines by decreasing SMADs expression level

Suppression of GSK3β by ERK mediates lipopolysaccharide induced cell migration in macrophage through β-catenin signaling

Bisindolyl Maleimides and Indolylmaleimide Derivatives—A Review of Their Synthesis and Bioactivity

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