Black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells.
Black raspberry-derived anthocyanins demethylate tumor suppressor genes through the inhibition of DNMT1 and DNMT3B in colon cancer cells.
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DOI：
10.1080/01635581.2013.741759
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Huang YW
中科院分区：
文献类型：
--
作者：
Wang LS;Kuo CT;Cho SJ;Seguin C;Siddiqui J;Stoner K;Weng YI;Huang TH;Tichelaar J;Yearsley M;Stoner GD;Huang YW
我们以前报道过，口服黑树莓粉可以降低结直肠癌患者肿瘤中抑癌基因的启动子甲基化。黑树莓中的花青素（AC）至少在一定程度上是其抑癌作用的原因。在本研究中，我们询问AC是否负责结直肠癌中观察到的去甲基化效应。0.5、5和25 μg/ml的AC处理3天抑制HCT 116、Caco 2和SW 480细胞中DNMT 1和DNMT 3B的活性和蛋白表达。Wnt通路上游的CDKN 2A、SFRP 2、SFRP 5和WIF 1的启动子被AC去甲基化。其中一些基因的mRNA表达增加。Wnt通路下游的β-catenin和c-Myc的mRNA表达减少，细胞增殖减少;凋亡增加。AC被摄取到HCT 116细胞中，并在使用共聚焦激光扫描显微镜观察的相同细胞中与DNMT 1和DNMT 3B差异定位。虽然有报道称DNMT 3B在小鼠淋巴瘤中受c-Myc调控，但在HCT 116细胞中DNMT 3B不与c-Myc结合。总之，我们的研究结果表明，AC是负责，至少部分，整个黑树莓在结直肠癌中的去甲基化作用。
We previously reported that oral administration of black raspberry powder decreased promoter methylation of tumor suppressor genes in tumors from patients with colorectal cancer. The anthocyanins (ACs) in black raspberries are responsible, at least in part, for their cancer-inhibitory effects. In the present study, we asked if ACs are responsible for the demethylation effects observed in colorectal cancers. Three days of treatment of ACs at 0.5, 5, and 25 μg/ml suppressed activity and protein expression of DNMT1 and DNMT3B in HCT116, Caco2 and SW480 cells. Promoters of CDKN2A, and SFRP2, SFRP5, and WIF1, upstream of Wnt pathway, were demethylated by ACs. mRNA expression of some of these genes was increased. mRNA expression of β-catenin and c-Myc, downstream of Wnt pathway, and cell proliferation were decreased; apoptosis was increased. ACs were taken up into HCT116 cells and were differentially localized with DNMT1 and DNMT3B in the same cells visualized using confocal laser scanning microscopy. Although it was reported that DNMT3B is regulated by c-Myc in mouse lymphoma, DNMT3B did not bind with c-Myc in HCT116 cells. In conclusion, our results suggest that ACs are responsible, at least in part, for the demethylation effects of whole black raspberries in colorectal cancers.
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影响因子：
11.2
作者：
Huang YW;Liu JC;Deatherage DE;Luo J;Mutch DG;Goodfellow PJ;Miller DS;Huang TH
通讯作者：
Huang TH
影响因子：
5.8
作者：
Whitley, AC;Stoner, GD;Walle, T
通讯作者：
Walle, T
影响因子：
11.2
作者：
Lin, Ruo-Kai;Wu, Chiu-Yi;Wang, Yi-Ching
通讯作者：
Wang, Yi-Ching
影响因子：
9.3
作者：
Ernst, I. M. A.;Wagner, A. E.;Rimbach, G.
通讯作者：
Rimbach, G.
影响因子：
2.9
作者：
HERTOG, MGL;HOLLMAN, PCH;KROMHOUT, D
通讯作者：
KROMHOUT, D