BCL-2 stimulates Apoptin-induced apoptosis

Adv Exp Med Biol. 1999;457:245-9. doi: 10.1007/978-1-4615-4811-9_26.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Capsid / toxicity*
  • Capsid Proteins*
  • Cell Transformation, Neoplastic
  • Chicken anemia virus
  • Humans
  • Leukemia
  • Lymphoma
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Capsid Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • VP3 protein, Chicken anemia virus