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 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.
Salti
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GI
University of Illinois at Chicago, College of Medicine, Department of Surgical Oncology (M/C 820), 840 South Wood Street, Chicago 60612, USA.
Grewal
S
S
Mehta
R R
RR
Das Gupta
T K
TK
Boddie
A W
AW
Constantinou
A I
AI
D015250:Aclarubicin / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000187:drug effects / Q000502:physiology; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D015250:Aclarubicin; D019833:Genistein; D004250:DNA Topoisomerases, Type II