Microsecond Pulsed Electric Fields: An Effective Way to Selectively Target and Radiosensitize Medulloblastoma Cancer Stem Cells

PurposeCancer stem cells constitute an endless reserve for the maintenance and progression of tumors, they could be reason conventional therapy failure. New therapeutic strategies are necessary to specifically target them. In this context, microsecond pulsed electric fields have been selected expose D283Med cells, a human medulloblastoma cell line resulted rich in cancer normal astrocytes.MethodsWe analyzed vitro different endpoints at times after field exposure, such as permeabilization, reactive oxygen species generation, viability/proliferation, cycle, clonogenicity, well expression genes involved apoptosis, senescence. Furthermore, response exposed was validated vivo heterotopic mouse xenograft model.ResultsOur results showed that specific pulse protocol (ie, 0.3 MV/m, 40 μs, 5 pulses) able induce irreversible membrane permeabilization apoptosis exclusively cells. surviving generation observed, together with transitory G2/M cell-cycle arrest senescence-associated phenotype via upregulation GADD45A. results, demonstrated significant tumor volume reduction no eradication mass. conjunction, we verified efficacy pre-exposure followed by ionizing irradiation enable complete inhibition growth.ConclusionsOur data reveal novel options targeting indicating nonionizing effective means overcome radioresistance Cancer astrocytes. We model. Our growth.