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

• Published in: European journal of cancer (1990) Vol. 36; no. 6; pp. 796 - 802
• Main Authors: Salti, G.I, Grewal, S, Mehta, R.R, Das Gupta, T.K, Boddie Jr, A.W, Constantinou, A.I
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-04-2000; Elsevier
• Subjects: Aclarubicin - pharmacology; Antibiotics, Antineoplastic - pharmacology; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - genetics; Biological and medical sciences; Cell Cycle - drug effects; Cell Division - drug effects; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Comet assay; DNA breakage; DNA Damage; DNA Topoisomerases, Type II - drug effects; DNA Topoisomerases, Type II - physiology; DNA, Neoplasm - drug effects; Dose-Response Relationship, Drug; Gastroenterology. Liver. Pancreas. Abdomen; Genistein; Genistein - pharmacology; Growth Inhibitors - pharmacology; Humans; Medical sciences; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Cells, Cultured; Tumors; Colon cancer; Genistein; Comet assay; DNA breakage; Apoptosis; Human; Cell culture; Malignant tumor; Experimental study; In vitro; Colonic disease; Breakage function; DNA; Digestive diseases; Intestinal disease; Colon; Biological effect
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(00)00017-4

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 μM) of genistein. Marked inhibition of HT-29 cell growth was evident at concentrations ranging from 60 to 150 μM. 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.