Arsenic Trioxide exerts cytotoxic and radiosensitizing effects in pediatric Medulloblastoma cell lines of SHH Subgroup
| العنوان: | Arsenic Trioxide exerts cytotoxic and radiosensitizing effects in pediatric Medulloblastoma cell lines of SHH Subgroup |
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| المؤلفون: | Luiz Gonzaga Tone, Rosane Gomes de Paula Queiroz, Pablo Ferreira das Chagas, Pamela Viani de Andrade, Paulo Henrique dos Santos Klinger, Elvis Terci Valera, Régia Caroline Peixoto Lira, Felipe Amstalden Trevisan, Carlos Alberto Scrideli, Ricardo Santos de Oliveira, Lara Elis Alberici Delsin, Augusto Faria Andrade, Gustavo Alencastro Veiga Cruzeiro |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-6 (2020) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Programmed cell death, Radiation-Sensitizing Agents, lcsh:Medicine, Apoptosis, FARMACOLOGIA, Article, chemistry.chemical_compound, Arsenic Trioxide, Cell Line, Tumor, Humans, Viability assay, Arsenic trioxide, Clonogenic assay, Cytotoxicity, Child, lcsh:Science, Multidisciplinary, Dose-Response Relationship, Drug, lcsh:R, Cell cycle, Neoplasm Proteins, CNS cancer, chemistry, Cell culture, Cancer research, lcsh:Q, Drug Screening Assays, Antitumor, Medulloblastoma |
| الوصف: | We evaluated the potential effects of ATO in different pediatric SHH-MB cell lines (ONS-76: TP53-wild type; DAOY and UW402: TP53-mutated). MB cell lines molecular subgroup was confirmed and TP53 mutations were validated. Cell viability, clonogenicity and apoptosis were evaluated after ATO treatment at different concentrations (1–16 µM) alone or combined with irradiation doses (0.5, 1, 2 and 4 Gy). Rad51 and Ku86 proteins were evaluated by WB. ATO treatment reduced cell viability for all SHH-MB cell lines. Significant decrease of clonogenic capacity and higher apoptosis rates were also observed after ATO exposure, being cell death more pronounced (>70%) for the SHH-MB TP53-mutated. Combined treatment of ATO with irradiation also reduced colonies formation in UW402 tumor cells, which was independent of DNA damage repair proteins Rad51 and Ku86. In silico analyses suggested that a set of genes from cell cycle and p53 pathways are differentially expressed in SHH tumor subtypes, suggesting that cell lines may respond to therapies according to the gene expression profiles. Herein, we showed ATO cytotoxicity in pediatric SHH cell lines, with marked radiosensitizing effect for the MB-SHH TP53-mutated cells. These results highlight the potential of ATO, alone or in combination with radiotherapy, supporting further clinical investigations. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0bedda3250e22daa120da0a65af09586Test http://link.springer.com/article/10.1038/s41598-020-63808-9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0bedda3250e22daa120da0a65af09586 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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