Role of Nrf2, HO-1 and GSH in neuroblastoma cell resistance to bortezomib
| العنوان: | Role of Nrf2, HO-1 and GSH in neuroblastoma cell resistance to bortezomib |
|---|---|
| المؤلفون: | Lorenzo Moretta, Nicola Traverso, Daniela Fenoglio, Umberto M. Marinari, Cinzia Domenicotti, Mario Salmona, Sabrina Piras, Maria Adelaide Pronzato, Anna Lisa Furfaro, A. De Luigi, Mariapaola Nitti |
| المصدر: | PLoS ONE, Vol 11, Iss 3, p e0152465 (2016) PLoS ONE |
| بيانات النشر: | Public Library of Science, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Transcription, Genetic, Cell, Cancer Treatment, Gene Expression, lcsh:Medicine, Artificial Gene Amplification and Extension, Biochemistry, Polymerase Chain Reaction, Antioxidants, Bortezomib, Neuroblastoma, chemistry.chemical_compound, Nucleic Acids, Medicine and Health Sciences, Enzyme assays, Colorimetric assays, lcsh:Science, Bioassays and physiological analysis, Cell Analysis, MTT assay, Multidisciplinary, GCLM, Glutathione, Up-Regulation, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, Research Article, medicine.drug, Cell Binding, Cell Physiology, Cell Viability Testing, Proteasome Endopeptidase Complex, Amino Acid Transport System y+, Cell Survival, NF-E2-Related Factor 2, Glutamate-Cysteine Ligase, Tretinoin, Biology, Promoter Regions, 03 medical and health sciences, Cell Line, Tumor, Genetics, medicine, Humans, Gene Regulation, Gene Silencing, RNA, Messenger, Viability assay, Molecular Biology Techniques, Molecular Biology, Dose-Response Relationship, Drug, lcsh:R, Biology and Life Sciences, Proteins, Protein Complexes, Proteasomes, DNA, Cell Biology, Reverse Transcriptase-Polymerase Chain Reaction, Molecular biology, Antioxidant Response Elements, Research and analysis methods, Heme oxygenase, Protein Subunits, 030104 developmental biology, chemistry, Proteasome, Drug Resistance, Neoplasm, Biochemical analysis, Cancer cell, Cancer research, lcsh:Q, Heme Oxygenase-1 |
| الوصف: | The activation of Nrf2 has been demonstrated to play a crucial role in cancer cell resistance to different anticancer therapies. The inhibition of proteasome activity has been proposed as a chemosensitizing therapy but the activation of Nrf2 could reduce its efficacy. Using the highly chemoresistant neuroblastoma cells HTLA-230, here we show that the strong reduction in proteasome activity, obtained by using low concentration of bortezomib (BTZ, 2.5 nM), fails in reducing cell viability. BTZ treatment favours the binding of Nrf2 to the ARE sequences in the promoter regions of target genes such as heme oxygenase 1 (HO-1), the modulatory subunit of γ-glutamylcysteine ligase (GCLM) and the transporter for cysteine (x-CT), enabling their transcription. GSH level is also increased after BTZ treatment. The up-regulation of Nrf2 target genes is responsible for cell resistance since HO-1 silencing and GSH depletion synergistically decrease BTZ-treated cell viability. Moreover, cell exposure to all-trans-Retinoic acid (ATRA, 3 μM) reduces the binding of Nrf2 to the ARE sequences, decreases HO-1 induction and lowers GSH level increasing the efficacy of bortezomib. These data suggest the role of Nrf2, HO-1 and GSH as molecular targets to improve the efficacy of low doses of bortezomib in the treatment of malignant neuroblastoma. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::94dd605498695e661ed10a73cedf4a48 http://hdl.handle.net/11567/840492 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....94dd605498695e661ed10a73cedf4a48 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |