Pharmacological inhibition of beta-catenin in hepatoblastoma cells

Ellerkamp, Verena; Lieber, Justus; Nagel, Casey; Wenz, Julia; Warmann, Steven W.; Fuchs, Jörg; Armeanu–Ebinger, Sorin

doi:10.1007/s00383-012-3237-9

Cited by 18 publications

(14 citation statements)

References 41 publications

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“…Similar to the effects of β-catenin knockdown, ICG-001 also caused significant growth suppression of lung cancer cells, which was consistent with with its reported function in Pancreateic cancer cells [18]. The IC 50 values of ICG-001 for H1299, A549 and H460 are 45.8µM, 41.4µM and 39.4µM respectively，which were similar to the study in hepatpcellular carcinoma cell lines [30]. Furthermore, ICG-001 regulated many genes altered by β-catenin knockdown, including MMP 9 and c-Myc.…”

Section: Discussionsupporting

confidence: 78%

β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells

Zheng

et al. 2017

Cell Physiol Biochem

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Background/Aims: β-catenin is an integral component of the canonical Wnt signaling pathway, and its mutations are an autosomal recessive cause of colorectal cancer (CRC), medulloblastoma (MDB), and ovarian cancer. Nevertheless, little is known about its function in lung cancers. Methods: We first knocked down β-catenin by siRNA to investigate its effects on lung cancer cell proliferation, migration and apoptosis. Then we verified the interaction between β-catenin and CREB binding protein (CBP) by immunofluoresence and co-immunoprecipition assays. Finally, the expression of β-catenin and CBP in human lung adenocarcinoma specimens were analyzed by immunohistochemistry assay. Results: β-catenin knockdown inhibited cell proliferation, promoted apoptosis and suppressed cell migration in A549 and H460 cells accompanied by the decreased expression of Myc, PCNA, VEGF, CD44, MMP-9, MMP-13 and activated bax/caspase-3 pathway. Furthermore, co-immunoprecipition and immunofluoresence analyses revealed that CBP interacted with β-catenin and contributed to β-catenin-mediated lung cancer cell growth. Abolishment of their interaction by the Wnt/β-catenin inhibitor ICG-001 remarkably suppressed cell proliferation. Immunohistochemistry assay of tissue microarrays from patients with lung cancer indicated that both CBP and β-catenin were highly expressed in tumor tissues and predicted poor prognosis in lung adenocarcinoma patients. Conclusions: Our study has provided new evidence for the role of β-catenin in promoting the growth of lung cancer cells through cooperation with CBP, and suggested that dual targeting of β-catenin and CBP could be a potential therapeutic strategy in lung cancer treatment.

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Section: Discussionsupporting

confidence: 78%

β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells

Zheng

et al. 2017

Cell Physiol Biochem

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“…To test this, we studied a specific pharmacological inhibitor of β-catenin signalling. The small molecule inhibitor ICG-001, in DMSO at 10 µM concentration 31,32 selectively blocks the β-catenin/CBP interaction, thereby interrupting a subset of TCF/β-catenin-mediated transcription activity and also reduced neurite outgrowth in PC-12 cells. In preclinical studies, ICG-001 was sufficient to inhibit tumor progression through attenuation of β-catenin/TCF-LEF signalling 33 .…”

Section: Resultsmentioning

confidence: 99%

Expression and Manipulation of the APC-β-Catenin Pathway During Peripheral Neuron Regeneration

Duraikannu

Martinez

Chandrasekhar

et al. 2018

Sci Rep

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Molecules and pathways that suppress growth are expressed in postmitotic neurons, a potential advantage in mature neural networks, but a liability during regeneration. In this work, we probed the APC (adenomatous polyposis coli)-β-catenin partner pathway in adult peripheral sensory neurons during regeneration. APC had robust expression in the cytoplasm and perinuclear region of adult DRG sensory neurons both before and after axotomy injury. β-catenin was expressed in neuronal nuclei, neuronal cytoplasm and also in perineuronal satellite cells. In injured dorsal root ganglia (DRG) sensory neurons and their axons, we observed paradoxical APC upregulation, despite its role as an inhibitor of growth whereas β-catenin was downregulated. Inhibition of APC in adult sensory neurons and activation of β-catenin, LEF/TCF transcriptional factors were associated with increased neuronal plasticity in vitro. Local knockdown of APC, at the site of sciatic nerve crush injury enhanced evidence for electrophysiological, behavioural and structural regeneration in vivo. This was accompanied by upregulation of β-catenin. Collectively, the APC-β-catenin-LEF/TCF transcriptional pathway impacts intrinsic mechanisms of axonal regeneration and neuronal plasticity after injury, offering new options for addressing axon regeneration.

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“…In further studies we recently showed an inhibitory influence of beta-catenin inhibitors on hepatoblastoma cells, modulating the nuclear localization of beta-catenin [ 15 ]. In HC-AFW1 cells, beta-catenin is located mainly in the nucleus and plays an important role in cell proliferation [ 16 ].…”

Section: Resultsmentioning

confidence: 99%

Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoproteinin vitroandin vivoinvolving the NFkappaB- and the beta-catenin pathways

et al. 2015

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In children with hepatocellular carcinoma (pHCC) the 5-year overall survival rate is poor. Effects of cytostatic therapies such as cisplatin and doxorubicin are limited due to chemoresistance and tumor relapse. In adult HCC, several antitumor properties are described for the use of curcumin. Curcumin is one of the best-investigated phytochemicals in complementary oncology without relevant side effects. Its use is limited by low bioavailability. Little is known about the influence of curcumin on pediatric epithelial hepatic malignancies. We investigated the effects of curcumin in combination with cisplatin on two pediatric epithelial liver tumor cell lines. As mechanisms of action inhibition of NFkappaB, beta-catenin, and decrease of cyclin D were identified. Using a mouse xenograft model we could show a significant decrease of alpha-fetoprotein after combination therapy of oral micellar curcumin and cisplatin. Significant concentrations of curcuminoids were found in blood samples, organ lysates, and tumor tissue after oral micellar curcumin administration. Micellar curcumin in combination with cisplatin can be a promising strategy for treatment of pediatric HCC.

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Pharmacological inhibition of beta-catenin in hepatoblastoma cells

Abstract: Pharmaceutical beta-catenin inhibitors can modulate the nuclear localization of beta-catenin and reduce cell viability of HB cells in vitro. These promising effects might optimize the outcome of high-risk HB. The orthotopic HB model is a suitable basis for further in vivo studies.

Cited by 18 publications

References 41 publications

β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells

β-Catenin Cooperates with CREB Binding Protein to Promote the Growth of Tumor Cells

Expression and Manipulation of the APC-β-Catenin Pathway During Peripheral Neuron Regeneration

Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoproteinin vitroandin vivoinvolving the NFkappaB- and the beta-catenin pathways

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