NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells Molecular Bases of Disease

In this study using RNA-Seq and bioinformatics analyses, we observed that NOTCH signaling is a deregulated pathway in enzalutamide-resistant cells. NOTCH2 and c-MYC gene expression positively correlated with AR expression in samples from patient with hormone refractory disease in which AR expression levels correspond to those typically observed in enzalutamide resistance. Cleaved NOTCH1, HES1 (Hes family BHLH transcription factor 1), and c-MYC protein expression levels are elevated in two enzalutamide-resistant cell lines, MR49F and C4-2R, indicating NOTCH signaling activation. Moreover, inhibition of the overexpressed ADAM metallopeptidase domain 10 (ADAM10) in the resistant cells induces an exclusive reduction in cleaved NOTCH1 expression. Furthermore, exposure of enzalutamide-resistant cells to both PF-03084014 and enzalutamide increased cell death, decreased colony formation ability, and resensitized cells to enzalutamide. Knockdown of NOTCH1 in C4-2R increased enzalutamide sensitivity by decreasing cell proliferation and increasing cleaved PARP expression. In a 22RV1 xenograft model, PF-03084014 and enzalutamide decreased tumor growth through reducing cell proliferation and increasing apoptosis. These results indicate that NOTCH1 signaling may contribute to enzalutamide resistance in prostate cancer, and inhibition of NOTCH signaling can resensitize resistant cells to enzalutamide.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research

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This study aims to investigate the apoptotic and anti-angiogenic effect of Zoledronic acid on hormone-refractory prostate cancer cell lines. XTT cell proliferation assay used to assess cytotoxicity. Caspase 3/7 activity and DNA fragmentation were measured to verify apoptosis. Angiogenic cytokine profiles investigated using the human angiogenesis antibody array I. Administration of Zoledronic acid on PC-3 and DU-145 prostate cancer cell lines resulted in increased cytotoxicity and apoptosis with a time- and dose-related manner. Also, the administration of Zoledronic acid significantly reduced several angiogenic cytokine pro...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
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Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
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Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
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Source: Brachytherapy - Category: Cancer & Oncology Authors: Source Type: research
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Source: Journal of Applied Clinical Medical Physics - Category: Physics Authors: Tags: J Appl Clin Med Phys Source Type: research
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Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
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Source: Medicine - Category: Internal Medicine Tags: Research Article: Study Protocol Systematic Review Source Type: research
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Source: Pathology Case Reviews - Category: Pathology Tags: Case Reviews Source Type: research
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