APOPTIN(R) SPECIFICALLY CAUSES APOPTOSIS IN TUMOR-CELLS AND AFTER UV-TREATMENT IN UNTRANSFORMED CELLS FROM CANCER-PRONE INDIVIDUALS - A REVIEW

Tumor formation is caused by an imbalance between cell replication and apoptosis, which is a physiological form of cell death. For instance, UV damage can result in tumor formation due to mutations of the tumor -suppressor gene p53, a major apoptosis-inducing protein. Over-express ion of the proto-oncogene Bcl-2, due to chromosomal translocation, can also inhibit apoptosis resulting in, e,g., lymphomas and leukemias. A nti-tumor therapies are often based on induction of apoptosis mediated via p53 and/or inhibited by Bcl-2, which explains the frequently poor results of anti-tumor treatment. The avian-virus-derived protein 'Apo ptin', induces apoptosis in a p53-independent way, is stimulated by Bc l-2 and is insensitive to BCR-ABL, another inhibitor of chemotherapeut ic agents. Apoptin induces apoptosis in human transformed/tumorigenic cells but not in normal diploid cells. Go-synthesis of SV40 large T an tigen and Apoptin results in induction of apoptosis, illustrating that the establishment of a stable transformed state is not required. UV-i rradiation causes an aberrant SOS-response in primary diploid cells fr om cancer-prone individuals and renders such cells susceptible to Apop tin-induced apoptosis. All these features make Apoptin a potential can didate as a therapeutic and diagnostic tool in cancer treatment. (C) 1 998 Elsevier Science B.V. All rights reserved.