Targeting MDM4/MDM2 binding interface for reactivation of p53 in cancer therapy

The aim of this experiment has been to investigate the transcriptional profile of HCT116 cells treated with Peptide-3 (Pep3) compared to untreated (NT), treated with solvent (DMSO) or with a mutated peptide (Pep3M) cells. Peptide-3 is a dodecapeptide able to interact with MDM2 at the levels of the interaction region of the MDM4 and MDM2 proteins, thereby interfering with the coopeartivy function of the proteins in the regulation of p53. This peptide is indeed able to specifically activate p53 and to cause apoptotis in different cancer cell lines and tumor growth inhibition in xenograft models. Three different experimental conditions have been analysed compared to untreated cells at time 0 (NT cells, the starting point of the treatment): cells treated with DMSO solvent (DMSO); treated with peptide-3 (Pep3) and with control peptide (Pep3M). The analysis has been performed at 24 and 48 hours after treatment. In addition, untreated cells after 24 hours of growth have been analysed as further control. All analyses have been performed in triplicates.