Depletion of drug-surviving glioma cells by a second phase treatment with low concentration of salinomycin

Standard treatment for glioma includes surgery, radiotherapy and chemotherapy but the outcome of patients is very poor. Antineoplastic drugs are usually administered alone or in combination for variable times (continuously or in cycles) in a single phase schedule. In this study we explored in vitro the antiproliferative effect of a 2 phases treatment. In the first phase, glioma cells where treated for 3-4 weeks with hydroxyurea (HU) or aphidicolin and then for 4 weeks with salinomycin, a drug that preferentially inhibits the proliferation of cancer stem cells. We found that salinomycin, is able to slowly deplete the fraction of glioma cells that survive the exposure to HU or aphidicolin. Surviving cells were killed at salinomycin concentrations lower than those required to kill untreated cells. The fraction of surviving cell showed traits of senescence including increased activity of the senescence associated -β-galactosidase (SA-β-gal) marker. Our data suggest that drug-induced senescent cells may constitute a novel target for cancer treatment and can be exploited in a two phases therapeutic regimen.