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

Abstract

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 determined by the ethidium bromide/acridine orange staining technique. DNA breakage was noted within 1 h of treatment. Apoptosis was only induced with high concentrations (>/=60 microM) of genistein. Marked inhibition of HT-29 cell growth was evident at concentrations ranging from 60 to 150 microM. 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 as the enzymatic target of genistein. Furthermore, topo II-mediated DNA cleavage is not required for the induction of apoptosis.

• Authors: G I Salti, S Grewal, R R Mehta, T K Das Gupta, A W Boddie Jr, A I Constantinou
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 36 Issue 6 Pg. 796-802 (Apr 2000) ISSN: 0959-8049 [Print] England
• PMID: 10762754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibiotics, Antineoplastic
• Antineoplastic Agents
• DNA, Neoplasm
• Growth Inhibitors
• Aclarubicin
• Genistein
• DNA Topoisomerases, Type II

Topics

• Aclarubicin (pharmacology)
• Antibiotics, Antineoplastic (pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (genetics)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Colonic Neoplasms (genetics, pathology)
• DNA Damage
• DNA Topoisomerases, Type II (drug effects, physiology)
• DNA, Neoplasm (drug effects)
• Dose-Response Relationship, Drug
• Genistein (pharmacology)
• Growth Inhibitors (pharmacology)
• Humans
• Tumor Cells, Cultured