Experimental Biology & Medicine, 2011, 236(6):714-722.

Genistein attenuates WNT signaling by up-regulating sFRP2 in a human colon cancer cell line

Yukun Zhang and Hong Chen

Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA

Colorectal cancer (CRC) is a leading fatal carcinoma worldwide. Our goal was to investigate the effects of genistein on WNT signaling, which is involved in colon epithelial cell growth and apoptosis. Human colon cancer cell line DLD-1 was treated for four days with 75 μmol/L genistein. Decreased nuclear β-catenin and increased phospho-β-catenin accumulation was detected, showing a change in WNT signaling. Reverse transcriptase-polymerase chain reaction analysis showed increased sFRP2 (a WNT pathway antagonist) mRNA expression following the genistein treatment. Methylation selective polymerase chain reaction showed decreased methylation in two CpG islands of the sFRP2 gene following genistein treatment, similar to the effect of 5-aza-cytidine, a demethylation agent. We observed reduced DLD-1 cell viability and increased apoptosis with genistein treatment. Genistein inhibits β-catenin-mediated WNT signaling through increasing sFRP2 gene expression by demethylating its silenced promoter in colon cancer cell line DLD-1.

英国《实验生物学与医学》，2010年6月

在人体结肠癌细胞中染料木黄酮通过上调 sFRP2抑制 WNT 信号

张玉坤，陈宏

美国伊利诺伊大学厄巴纳-尚佩恩分校食品科学和人类营养学院

大肠癌 (CRC) 是全球排名靠前的致命癌症。我们的目标是探究大豆异黄酮对参与结肠上皮细胞生长和凋亡的 WNT 信号的作用。用75 umol/L染料木黄酮处理人体结肠癌细胞 DLD-1四天。检测到细胞核 β-连环蛋白的降低和磷酸基-β-连环蛋白堆积物的增加，表明 WNT 信号的变化。在经过金雀异黄素治疗后，逆转录-聚合酶链反应的分析表明提高了 sFRP2 （一种WNT 途径的拮抗剂）的 mRNA 表达。甲基化选择性聚合酶链反应表明染料木黄酮治疗以后，在sFRP2 基因的两个 CpG 岛中甲基化程度下降，与去甲基化试剂5-氮杂胞苷的效果相似。我们观察到染料木黄酮可以使DLD-1细胞活性降低和细胞凋亡增加。在结肠癌细胞 DLD-1中染料木黄酮通过去甲基化沉默启动子提高 sFRP2 基因表达来抑制 β-连环蛋白-介导的 WNT 信号。