Ca2+/Mg(2+)-dependent endonuclease activation is an early event in VP-16-induced apoptosis of human breast cancer MCF7 cells in vitro.

Apoptosis is now recognized as one of the major processes regulating the size of cell populations. However, despite intensive investigations the biochemical and enzymological mechanisms involved in apoptosis remain unclear. In the present study we demonstrate activation of a Ca2+/Mg(2+)-dependent endonuclease during VP-16-induced apoptosis in MCF7 cells. Nuclease activation occurred prior to the appearance of internucleosomal DNA fragmentation, suggesting that this activation may be an early and possibly critical step in drug-induced apoptosis. Analysis of the internucleosomal DNA fragments showed that they contained phosphorylated 5'-ends, indicating that they were produced by a Ca2+/Mg(2+)-dependent endonuclease.