Cell Death & Differentiation, 2007, 14(3):472-9.

Genistein inhibits Brca1 mutant tumor growth through activation of DNA damage checkpoints, cell cycle arrest, and mitotic catastrophe

Y Tominaga, A Wang , R H Wang, et al

Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

Epidemiological studies revealed that amount of consumption of soy was inversely related to incidence of breast cancer. Genistein, the predominant isoflavone in soy, has been reported to reduce the incidence of breast cancer in animal models. To investigate whether genistein has a therapeutic effect on BRCA1-associated breast cancer, we treated Brca1 mutant mammary tumor cells with genistein. We showed that genistein treatment depleted the G1 population of cells, which was accompanied by an accumulation of cells at G2. Some genistein-treated cells entered mitosis; however, they exhibited chromosome abnormalities and maintained tetraploidy owing to abortive mitotic exit. A fraction of G2 cells underwent endoreduplication and became polyploid, which was accompanied by increased cell death through activating DNA damage response. Furthermore, our data indicated that Brca1 mutant cells were more sensitive to genistein than some other types of cancer cells, highlighting a good therapeutic potential of genistein for BRCA1-associated breast cancer.

英国《细胞死亡与分化》，2007年

金雀异黄素通过激活DNA损伤检查点，细胞周期停滞和有丝分裂停止来抑制Brca1突变体的肿瘤生长

富永 Y，王A，王RH，等

美国国家卫生研究院国家糖尿病与消化和肾脏疾病研究所发展与疾病分科遗传学，美国

流行病学研究显示，大豆消费量与乳腺癌发病率呈负相关。据报道，染料木黄酮是大豆中主要的异黄酮，据报道在动物模型中降低乳腺癌的发病率。为了研究染料木素对BRCA1相关乳腺癌有治疗作用，我们用染料木素处理Brca1突变体乳腺肿瘤细胞。我们显示染料木素处理耗尽了G1细胞群体，伴随着G2细胞的积累。一些染料木素处理的细胞进入有丝分裂;然而，它们显示出染色体异常并且由于流产有丝分裂出口而保持四倍体。 G2细胞的一小部分进行内切复制，并成为多倍体，伴随着通过激活DNA损伤反应增加细胞死亡。此外，我们的数据表明Brca1突变体细胞比一些其他类型的癌细胞对染料木素更敏感，突出了BRCA1相关乳腺癌染料木素的良好治疗潜力。