Apoptosis is a physiological mechanism for eliminating superfluous, altered or transformed cells without eliciting damage to normal cells or surrounding tissues. It has become evident that tumor growth is regulated not only by the rate at which tumor cells divide but also by the rate at which they undergo apoptosis. At present, several (chemo)therapeutic agents are known to exert their lethal action by apoptosis.Recently, we have identified a novel protein, which is encoded by gene VP3 of chicken anemia virus (CAV) and which causes apoptosis in chicken T cells. The protein which we call apoptin, is a polypeptide of 121 amino acids, and contains proline-rich and basic regions. Removal of C-terminal basic amino acids from apoptin resulted in partial translocation of apoptin into the cytoplasm and a significant reduction in its apoptotic activity.We have demonstrated that apoptin can induce apoptosis in cell lines derived from human leukemias and lymphomas, or in EBV-immortalized B cells. Two of these cell lines are known to express the proto-oncogene bcl-2, which might be involved in the inhibition of apoptosis. We are investigating the possibility to use the expression of apoptin as a potential anti-cancer therapy for hematologic tumors.It has been reported by others that p53 acts as an intermediate in specific apoptotic pathways. Unfortunately, large number of tumors acquire a mutation in p53 during their development, which often correlates with a poor response to anti-cancer therapy. To examine whether apoptin-induced apoptosis takes place via the p53 pathway, apoptin was expressed in cells derived from human osteosarcoma cell lines that either lack the gene for p53, harbor a mutated p53 gene, or contain wild-type p53. In all 3 cell lines expression of apoptin induces apoptosis. Apparently, apoptin-induced apoptosis is not mediated by p53, which suggests that apoptin may also induce apoptosis in tumors lacking (functional) p53.At present, we are developing (viral) gene-therapy strategies to specifically deliver the genetic information for apoptin to tumor cells.