核分裂突变
雷达51
有丝分裂
细胞凋亡
细胞周期检查点
细胞周期
癌症研究
DNA修复
DNA损伤
程序性细胞死亡
生物
细胞生物学
癌细胞
细胞生长
活力测定
激酶
化学
癌症
DNA
遗传学
作者
Laura Mosca,Cristina Pagano,Roberta Veglia Tranchese,Roberta Grillo,Francesca Cadoni,Giovanna Navarra,Laura Coppola,Mario Pagano,Luigi Mele,Giovanna Cacciapuoti,Chiara Laezza,Marina Porcelli
出处
期刊:Molecules
[MDPI AG]
日期:2024-04-10
卷期号:29 (8): 1708-1708
标识
DOI:10.3390/molecules29081708
摘要
Glioblastoma (GBM), the most frequent and lethal brain cancer in adults, is characterized by short survival times and high mortality rates. Due to the resistance of GBM cells to conventional therapeutic treatments, scientific interest is focusing on the search for alternative and efficient adjuvant treatments. S-Adenosylmethionine (AdoMet), the well-studied physiological methyl donor, has emerged as a promising anticancer compound and a modulator of multiple cancer-related signaling pathways. We report here for the first time that AdoMet selectively inhibited the viability and proliferation of U87MG, U343MG, and U251MG GBM cells. In these cell lines, AdoMet induced S and G2/M cell cycle arrest and apoptosis and downregulated the expression and activation of proteins involved in homologous recombination DNA repair, including RAD51, BRCA1, and Chk1. Furthermore, AdoMet was able to maintain DNA in a damaged state, as indicated by the increased γH2AX/H2AX ratio. AdoMet promoted mitotic catastrophe through inhibiting Aurora B kinase expression, phosphorylation, and localization causing GBM cells to undergo mitotic catastrophe-induced death. Finally, AdoMet inhibited DNA repair and induced cell cycle arrest, apoptosis, and mitotic catastrophe in patient-derived GBM cells. In light of these results, AdoMet could be considered a potential adjuvant in GBM therapy.
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