期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 14, 页码 -出版社
MDPI
DOI: 10.3390/ijms241411286
关键词
glioblastoma stem cells (GSCs); glioblastoma multiforme (GBM); nitric oxide (NO); Temozolomide (TMZ); cytostasis; adjuvant treatment
Glioblastoma multiforme (GBM) has high mortality and recurrence rates. Glioblastoma Stem Cells (GSCs) contribute to malignancy resilience. Nitric Oxide (NO) has shown anti-cancer efficacy in GBM cells and can enhance the sensitivity of GSCs to TMZ.
Glioblastoma multiforme (GBM) has high mortality and recurrence rates. Malignancy resilience is ascribed to Glioblastoma Stem Cells (GSCs), which are resistant to Temozolomide (TMZ), the gold standard for GBM post-surgical treatment. However, Nitric Oxide (NO) has demonstrated anti-cancer efficacy in GBM cells, but its potential impact on GSCs remains unexplored. Accordingly, we investigated the effects of NO, both alone and in combination with TMZ, on patient-derived GSCs. Experimentally selected concentrations of diethylenetriamine/NO adduct and TMZ were used through a time course up to 21 days of treatment, to evaluate GSC proliferation and death, functional recovery, and apoptosis. Immunofluorescence and Western blot analyses revealed treatment-induced effects in cell cycle and DNA damage occurrence and repair. Our results showed that NO impairs self-renewal, disrupts cell-cycle progression, and expands the quiescent cells' population. Consistently, NO triggered a significant but tolerated level of DNA damage, but not apoptosis. Interestingly, NO/TMZ cotreatment further inhibited cell cycle progression, augmented G0 cells, induced cell death, but also enhanced DNA damage repair activity. These findings suggest that, although NO administration does not eliminate GSCs, it stunts their proliferation, and makes cells susceptible to TMZ. The resulting cytostatic effect may potentially allow long-term control over the GSCs' subpopulation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据