Overall, our results provide evidence that the impairment of PC cell clonogenicity, paralleled by the decrease in CD133+EpCAM+ cancer stem-like PC cell subpopulation, together with DNA damage, apoptosis, and interference in cell cycle progression all contribute to the antiproliferative effects displayed by the DF5 derivative, with distinct effects in the three PC cell lines. This evidence concerns the gene PROM1 and pachyonychia congenita.