Pifithrin-α is firstly found to block the activation of p53-responsive lacZ in ConA cells and reduce activation of endogenous cellular p53-responsive genes. In MEF cells transformed with E1a+ras, 10μM Pifithrin-α can inhibit the apoptosis of the cells and this anti-apoptotic activity is p53-dependent. Pifithrin-α also inhibits the growth arrest of human diploid fibroblasts induced by DNA damage but has no effect on p53-deficient fibroblasts. In addition, Pifithrin-α induces G2-arrest of cells after gamma irradiation.