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Glioblastoma multiforme (GBM) is a very aggressive type of primary brain tumor in adults with a poor prognosis. DNA double-strand breaks are known to be associated with the development of numerous cancer types due to their ability to generate genomic instabilities. In GBM, the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is a common pathway that can be activated by exogenous and endogenous factors. Genomic instability may be an endogenous stimulating factor for activation of the PI3K/Akt pathway, which may inhibit the apoptosis of GBM cells. Spontaneous DNA double-strand breaks play an essential role in the survival of GBM cells, and apoptosis levels may reflect survival ability. However, no study has yet been conducted to analyse the association between spontaneous DNA double-strand breaks and apoptosis in patients with GBM prior to treatment. Therefore, the present study examined the concentrations of γ-histone 2AX (γ-H2AX), a sensitive marker of spontaneous DNA double-strand breaks, and cleaved caspase-3, a marker of apoptosis, in patients with GBM. The correlation of γ-H2AX with cleaved caspase-3, PI3K and Akt was also investigated. A total of 26 pre-treatment tumor tissue specimens from patient with GBM were analyzed to determine the concentrations of γ-H2AX, PI3K, Akt and cleaved caspase-3 using sandwich enzyme-linked immunosorbent assays. The results showed a moderate positive correlation between γ-H2AX and PI3K (r=0.52; P=0.007), a moderate positive correlation between γ-H2AX and Akt (r=0.4; P=0.041) and a strong negative correlation between γ-H2AX and cleaved caspase-3 (r=-0.61; P=0.0009). These analyses were also performed in seven tumor tissue specimens from patients with grade I glioma as controls, but no significant correlations were detected. The findings of the present study suggest that a high level of γ-H2AX may affect GBM cell apoptosis via the PI3K/Akt pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2023, Spandidos Publications.)

Cancer stem cells (CSCs) are a subpopulation of cancer cells responsible for tumor maintenance and relapse due to their ability to resist various anticancer effects. Owing to the resistance of CSCs to the effects of targeted therapy, an alternative strategy that targets post-translational glycosylation may be an improved approach to treat cancer as it disrupts multiple coordinated signaling that maintains the stemness of CSCs. Glucosamine acts as an anticancer agent possibly by inhibiting N-linked glycosylation. The aim of the present study was to investigate the effect of glucosamine on the stemness of breast CSCs, which is regulated by signal transducer and activator of transcription 3 (STAT3) signaling. Human aldehyde dehydrogenase-positive (ALDH + ) breast CSCs and MCF7 cells were treated with various concentrations (0.25, 1 or 4 mM) of glucosamine for 24 h. Subsequently, cell viability was determined by performing a trypan blue exclusion assay, pluripotency gene [ALDH 1 family member A1 ( ALDH1A1 ), octamer-binding transcription factor 4 ( OCT-4 ), and Krüppel-like factor 4 ( KLF4 )] expression was determined using the reverse transcription-quantitative polymerase chain reaction, and STAT3 and phosphorylated STAT3 (pSTAT3) levels were determined by performing western blot analysis. Furthermore, the number of mammosphere-forming units (MFUs) in ALDH + breast CSCs and MCF7 cells was determined. It was determined that glucosamine treatment decreased the viability of ALDH + breast CSCs. Glucosamine treatment also decreased the stemness of ALDH + breast CSCs and MCF7 cells, as indicated by decreased ALDH1A1, OCT-4 and KLF4 expression level, and a decreased number of MFUs. This effect of glucosamine may be associated with a decreased pSTAT3/STAT3 ratio, indicating that glucosamine inhibited STAT3 activation; therefore, the results of the present study indicated that glucosamine treatment may be an improved approach to target the stemness of CSCs.