The G-quadruplex-stabilizing ligand RHPS4 enhances sensitivity of U251MG glioblastoma cells to clinical carbon ion beams

The FEBS Journal
Francesco BerardinelliAntonio Antoccia

Abstract

The pentacyclic acridine RHPS4 is a highly potent and specific G-quadruplex (G4) ligand, which binds and stabilizes telomeric G4 leading to the block of the replication forks at telomeres and consequently to telomere dysfunctionalization. In turn, the cell recognizes unprotected telomeres as DNA double-strand breaks with consequent activation of DNA repair response at telomeres, cellular growth impairment, and death. Data from the literature showed the capability of this compound to sensitize U251MG glioblastoma radioresistant cell line to X-rays sparsely ionizing radiations. In the present paper, it was investigated whether RHPS4 is also able to increase the effect of clinical carbon ion beams (cells irradiated in the middle of a spread-out Bragg peak, in the energy range of 246-312 MeV·μm-1 and a dose-averaged linear energy transfer of 46 keV·μm-1 ). Interestingly, also for charged particles whose damage inflicted to DNA is more complex than that of sparsely ionizing radiations and results in higher Relative Biological Effectiveness (RBE), RHPS4 significantly potentiated the radiation effect in terms of cell killing, delayed rejoining of DNA double-strand breaks (γ-H2AX and 53BBP1 immunofluorescence staining), chromosome aber...Continue Reading

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