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首页> 外文期刊>The Journal of Nutritional Biochemistry >Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells
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Anthocyanin-containing purple-fleshed potatoes suppress colon tumorigenesis via elimination of colon cancer stem cells

机译：含花青素的紫色肉土豆通过消除结肠癌干细胞来抑制结肠肿瘤发生

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摘要

Cancer stem cells (CSCs) are shown to be responsible for initiation and progression of tumors in a variety of cancers. We previously showed that anthocyanin-containing baked purple-fleshed potato (PP) extracts (PA) suppressed early and advanced human colon cancer cell proliferation and induced apoptosis, but their effect on colon CSCs is not known. Considering the evidence of bioactive compounds, such as anthocyanins, against cancers, there is a critical need to study anticancer activity of PP, a global food crop, against colon CSCs. Thus, isolated colon CSCs (positive for CD44, CD133 and ALDH1b1 markers) with functioning p53 and shRNA-attenuated p53 were treated with PA at 5.0 mu g/ml. Effects of baked PP (20% wt/wt) against colon CSCs were also tested in vivo in mice with azoxymethane-induced colon tumorigenesis. Effects of PA/PP were compared to positive control sulindac. In vitro, PA suppressed proliferation and elevated apoptosis in a p53-independent manner in colon CSCs. PA, but not sulindac, suppressed levels of Wnt pathway effector beta-catenin (a critical regulator of CSC proliferation) and its downstream proteins (c-Myc and cyclin D1) and elevated Bax and cytochrome c, proteins-mediating mitochondrial apoptosis. In vivo, PP reduced the number of crypts containing cells with nuclear beta-catenin (an indicator of colon CSCs) via induction of apoptosis and suppressed tumor incidence similar to that of sulindac. Combined, our data suggest that PP may contribute to reduced colon CSCs number and tumor incidence in vivo via suppression of Wnt/beta-catenin signaling and elevation of mitochondria-mediated apoptosis. (C) 2015 Elsevier Inc. All rights reserved.
机译：癌症干细胞（CSC）被证明与多种癌症中肿瘤的发生和发展有关。我们以前显示含花青素的烤紫肉马铃薯（PP）提取物（PA）抑制了早期和晚期人类结肠癌细胞的增殖并诱导了细胞凋亡，但是它们对结肠CSC的作用尚不清楚。考虑到花青素等生物活性化合物具有抗癌作用的证据，迫切需要研究全球粮食作物PP对结肠CSC的抗癌活性。因此，将具有功能性p53和shRNA减毒的p53的分离的结肠CSC（CD44，CD133和ALDH1b1标记阳性）用PA以5.0μg/ ml处理。还在具有乙氧基甲烷诱导的结肠肿瘤发生的小鼠体内测试了烘烤的PP（20％wt / wt）对结肠CSC的作用。将PA / PP的作用与阳性对照舒林酸进行了比较。在体外，PA以独立于p53的方式抑制结肠CSC中的增殖并增加凋亡。 PA，但不是舒林酸，抑制了Wnt途径效应子β-catenin（CSC增殖的关键调节剂）及其下游蛋白（c-Myc和cyclin D1）的水平，并抑制了Bax和细胞色素c的升高，即介导线粒体凋亡的蛋白。在体内，PP通过诱导凋亡减少了含有核β-连环蛋白（结肠CSC的指标）的细胞隐窝的数量，并抑制了与舒林酸相似的肿瘤发生率。结合起来，我们的数据表明PP可能通过抑制Wnt /β-catenin信号传导和线粒体介导的细胞凋亡的升高来降低结肠CSC的数量和体内肿瘤的发生率。 （C）2015 Elsevier Inc.保留所有权利。

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