Early disruption of mitochondrial membrane potential, as evidenced by time-lapse fluorescence microscopy and TEM, together with later production of ROS, cleavage of caspase-9, caspase-3, the PARP, upregulation of Bax and downregulation of Bcl-2 were effects induced by Rb44L1, and they are all consistent with the intrinsic pathway of apoptosis (53, 54), strongly suggesting that this is the main in vitro cytotoxic mechanism of the peptide in melanoma cells. This evidence concerns the gene CASP3 and melanoma.