Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells.
Genistein induces apoptosis and topoisomerase II-mediated DNA breakage in colon cancer cells.
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DOI：
10.1016/s0959-8049(00)00017-4
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发表时间：
2000-04
影响因子：
8.4
通讯作者：
G. Salti;S. Grewal;R. Mehta;T. K. Das Gupta;A. Boddie;A. Constantinou
中科院分区：
文献类型：
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作者：
G. Salti;S. Grewal;R. Mehta;T. K. Das Gupta;A. Boddie;A. Constantinou
本研究旨在确定 (a) 金雀异黄素是否会在 HT-29 结肠癌细胞中诱导拓扑 II 介导的 DNA 损伤； (b) 这种损伤是否是诱导细胞凋亡所必需的。使用彗星试验评估 DNA 损伤。通过溴化乙锭/吖啶橙染色技术测定细胞凋亡。处理后 1 小时内观察到 DNA 断裂。仅用高浓度（⩾60 μM）金雀异黄素诱导细胞凋亡。在 60 至 150 μM 的浓度范围内，对 HT-29 细胞生长的显着抑制是显而易见的。这与 G2/M 细胞周期停滞有关。在 SW-620 和 SW-1116 结肠癌细胞系中也获得了类似的结果。 Aclarubicin 是一种拓扑 II 拮抗剂，可减少金雀异黄素诱导的 DNA 断裂，但不会减少细胞凋亡。这些数据表明，在结肠癌细胞中，拓扑 II 是金雀异黄酮的酶促靶点。此外，诱导细胞凋亡不需要拓扑 II 介导的 DNA 切割。
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 G2/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.