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BCL-2 Stimulates Apoptin®-Induced Apoptosis

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Drug Resistance in Leukemia and Lymphoma III

Abstract

Apoptin, a protein encoded by an avian virus, induces apoptosis in various cultured human tumorigenic and/or transformed cell lines, e.g. in leukemia, lymphoma or EBV-transformed B cells. In such cells, Apoptin induces p53-independent apoptosis, and the proto-oncogene Bcl-2 accelerates this effect. The latter is surprising for, in general, Bcl-2 is known to inhibit e.g., p53-induced apoptosis. On the other hand, in normal non-transformed human cells, Apoptin is unable to induce apoptosis, even when Bcl-2 is over-expressed. In normal cells, Apoptin is found predominantly in the cytoplasm, whereas in tumor cells it is located in the nucleus. Cellular-localization studies showed that Apoptin is not located in mitochondria, indicating once more that Bcl-2 does not interfere with Apoptin in normal cells. In animal models Apoptin appears to be a safe and efficient anti-tumor agent. These data, in continuation with the observations that Apoptin is specifically stimulated by Bcl-2 in tumor cells, does not need p53, and is not inhibited by BCR-ABL in these cells, imply that Apoptin holds the promise of being the basis for anti-tumor therapy.

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© 1999 Springer Science+Business Media New York

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Danen-Van Oorschot, A.A.A.M., van der Eb, A.J., Noteborn, M.H.M. (1999). BCL-2 Stimulates Apoptin®-Induced Apoptosis. In: Kaspers, G.J.L., Pieters, R., Veerman, A.J.P. (eds) Drug Resistance in Leukemia and Lymphoma III. Advances in Experimental Medicine and Biology, vol 457. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4811-9_26

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  • DOI: https://doi.org/10.1007/978-1-4615-4811-9_26

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7180-9

  • Online ISBN: 978-1-4615-4811-9

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