Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells

The present study was undertaken to determine if (a) genistein induces topo II-mediated DNA damage in HT-29 colon cancer cells: and (b) if this damage is required to induce apoptosis. DNA damage was evaluated using the comet assay. Apoptosis was deter-mined by the ethidium bromide/acridine orange staining technique. DNA breakage was noted within 1 h of treatment. Apoptosis was only induced with high concentrations (greater than or equal to 60 mu M) of genistein. Marked inhibition of HT-29 cell growth was evident at concentrations ranging from 60 to 150 mu M. This was associated with a cell cycle arrest at G(2)-/M. Similar findings were obtained in SW-620 and SW-1116 colon cancer cell lines. Aclarubicin, a topo II antagonist, reduced genistein-induced DNA breaks but did not reduce apoptosis. These data suggest that. in colon cancer cells, topo II serves us the enzymatic target of genistein. Furthermore, topo II-mediated DNA cleavage is not required for the induction of apoptosis. (C) 2000 Published by Elsevier Science tld. All rights reserved.