Consequently, inhibiting Ca2+ efflux (using BAPTA-AM) resulted in restoring the malignant phenotype of A375 and COLO-679 malignant melanoma cells through inhibiting the activation of initiator caspase-9 and effector caspase-3, thereby highlighting the role of Ca2+ efflux as a key intracellular mediator in signaling the PhEF-induced activation of intrinsic apoptosis. This evidence concerns the gene CASP3 and melanoma.