Effects of the Combined Treatment with a G-Quadruplex-Stabilizing Ligand and Photon Beams on Glioblastoma Stem-like Cells: A Magnetic Resonance Study

by Selleckchem | Jul 19 2023

Glioblastoma multiforme is a malignant primary brain tumor with a poor prognosis and high rates of chemo-radiotherapy failure, mainly due to a small cell fraction with stem-like properties (GSCs). The mechanisms underlying GSC response to radiation need to be elucidated to enhance sensitivity to treatments and to develop new therapeutic strategies. In a previous study, two GSC lines, named line #1 and line #83, responded differently to carbon ions and photon beams, with the differences likely attributable to their own different metabolic fingerprint rather than to radiation type. Data from the literature showed the capability of RHPS4, a G-quadruplex stabilizing ligand, to sensitize the glioblastoma radioresistant U251MG cells to X-rays. The combined metabolic effect of ligand #190, a new RHPS4-derivative showing reduced cardiotoxicity, and a photon beam has been monitored by magnetic resonance (MR) spectroscopy for the two GSC lines, #1 and #83, to reveal whether a synergistic response occurs. MR spectra from both lines were affected by single and combined treatments, but the variations of the analysed metabolites were statistically significant mainly in line #1, without synergistic effects due to combination. The multivariate analysis of ten metabolites shows a separation between control and treated samples in line #1 regardless of treatment type, while separation was not detected in line #83.

Comments:

The study investigated the response of two different glioblastoma stem cell (GSC) lines, named line #1 and line #83, to radiation therapy and the potential synergistic effects of a G-quadruplex stabilizing ligand, specifically ligand #190, in combination with photon beam radiation. The aim was to understand the mechanisms underlying the response of GSCs to radiation and explore new therapeutic strategies for glioblastoma treatment.

The previous study had shown that the two GSC lines, #1 and #83, responded differently to carbon ions and photon beams. The differences in response were attributed to their distinct metabolic fingerprints rather than the type of radiation used. This suggests that the metabolic characteristics of GSCs play a significant role in their response to radiation therapy.

In the current study, the researchers investigated the combined metabolic effect of ligand #190 and photon beam radiation using magnetic resonance (MR) spectroscopy. MR spectra were obtained for both GSC lines, and the variations in metabolites were analyzed and compared statistically.

The results showed that the MR spectra of both GSC lines were affected by single and combined treatments. However, the variations in metabolites were statistically significant mainly in line #1, indicating a more pronounced response to the treatments in this cell line. Importantly, the study did not observe synergistic effects resulting from the combination of ligand #190 and photon beam radiation in either GSC line.

Furthermore, multivariate analysis of ten metabolites demonstrated a clear separation between control and treated samples in line #1, irrespective of the treatment type. However, such separation was not observed in line #83, suggesting that the metabolic response to the treatments might be different in these two GSC lines.

In summary, this study highlighted the differential response of GSC lines to radiation therapy and the potential influence of their metabolic fingerprints on treatment outcomes. While line #1 exhibited statistically significant variations in metabolites upon treatment, indicating sensitivity to the interventions, line #83 did not show such distinct metabolic changes. The investigation did not find synergistic effects resulting from the combination of ligand #190 and photon beam radiation in either GSC line. These findings contribute to the understanding of glioblastoma treatment resistance mechanisms and emphasize the importance of personalized approaches in developing effective therapeutic strategies.