International Journal of Oncology, 2013, 43(4):1117-24.

Inhibitory effects of a major soy isoflavone, genistein, on human DNA topoisomerase II activity and cancer cell proliferation

Yoshiyuki Mizushina, Kazuaki Shiomi, Isoko Kuriyama, et al

Laboratory of Food and Nutritional Sciences, Faculty of Nutrition, Kobe Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan

The inhibitory activity of 3 soy isoflavones (daidzein, genistein and glycitein) and their glycosides (daidzin, genistin and glycitin) on mammalian DNA polymerases (pols) and topoisomerases (topos) was investigated. Of the compounds tested, only genistein selectively inhibited human topo II activity and had an IC50 value of 37.5 µM. These isoflavones had no effect on the activity of human topo I; mammalian pols α, β, γ and κ; or on any other DNA metabolic enzyme tested. Thermal transition analysis indicated that genistein did not influence the direct binding to double-stranded DNA. Genistein prevented the proliferation of HCT116 human colon carcinoma cells with an LD50 of 94.0 µM and it halted the cell cycle in G2/M phase. These results suggest that decreases in cell proliferation due to genistein may result from the inhibition of cellular topo II and that genistein, a major soy isoflavone, may be an anticancer food component. The relationship between the structures and these bioactivities of soy isoflavones is discussed.

希腊《国际肿瘤学杂志》，2013年10月

一种主要的大豆异黄酮，金雀异黄素，对人类 DNA 拓扑异构酶 II 活性和肿瘤细胞增殖的抑制作用

水品吉行，潮见池田，栗山伊索科，等

日本神户关西大学营养学院食品与营养科学实验室

研究了 3种 大豆异黄酮 （大豆甙元、 金雀异黄素和黄豆黄素） 和其糖苷 （大豆苷元、 染料木苷和黄豆黄苷） 对哺乳动物 DNA 聚合酶 （pols） 和拓扑异构酶 (topos) 的抑制活性。在测试的化合物中，只有金雀异黄素选择性地抑制了人类拓扑异构酶II的活性并且IC50 的值为37.5 µM。这些异黄酮对人类拓扑异构酶I；哺乳动物的聚合酶α、 β、 γ 和 κ；或任何其他测试的 DNA 代谢酶的活性没有影响。热转变分析表明，金雀异黄素不影响到双链 DNA的直接绑定。金雀异黄素与94.0 µM的 LD50共同阻止了HCT116 人体结肠癌细胞的增殖，并使其在 G2/M 期细胞周期停滞。这些结果表明由于金雀异黄素抑制细胞拓扑异构酶 II造成细胞增殖的减弱，并且，金雀异黄素，一种主要的大豆异黄酮，可能是一种抗癌食物营养成分。讨论了这些大豆异黄酮的结构与生物活性之间的关系。