Pisosterol induces G2/M cell cycle arrest and apoptosis via the ATM/ATR signaling pathway in human glioma cells
| Autor: | Rommel Rodríguez Burbano, Edivaldo Herculano Corrêa de Oliveira, Bárbara do Nascimento Borges, Maria L. Harada, Cláudia Pessoa, Wallax Augusto Silva Ferreira |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
Antineoplastic Agents Apoptosis Ataxia Telangiectasia Mutated Proteins Neoplasias Encef?licas / tratamento farmacol?gico Glioma / tratamento farmacol?gico 03 medical and health sciences 0302 clinical medicine p14arf Cell Line Tumor Glioma medicine Humans Viability assay CHEK1 Neoplasias Encef?licas 030304 developmental biology Pharmacology 0303 health sciences Cyclin-dependent kinase 1 Ciclo Celular Terpenes Cell growth Chemistry Basidiomycota Cell cycle medicine.disease Ensaios de Sele??o de Medicamentos Antitumorais / m?todos G2 Phase Cell Cycle Checkpoints Compostos Qu?micos / an?lise 030220 oncology & carcinogenesis Cancer research Molecular Medicine Signal Transduction |
| Zdroj: | Repositório Digital do Instituto Evandro Chagas (Patuá) Instituto Evandro Chagas (IEC) instacron:IEC |
| Popis: | Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecidos e Citogen?tica Ananindeua, PA, Brasil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Citogen?tica Humana. Bel?m, PA, Brazil. Universidade Federal do Cear?. Departamento de Fisiologia e Farmacologia. Fortaleza, CE, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Biologia Molecular Francisco Mauro Salzano. Bel?m, PA, Brazil. Universidade Federal do Par?. Instituto de Ci?ncias Biol?gicas. Laborat?rio de Biologia Molecular Francisco Mauro Salzano. Bel?m, PA, Brazil. Universidade Federal do Par?. Faculdade de Ci?ncias Naturais. Instituto de Ci?ncias Exatas e Naturais. Bel?m, PA, Brazil. Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, we reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: We, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggest that this compound might be a promising anticancer candidate for further investigation. |
| Databáze: | OpenAIRE |
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