Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells
Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells
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DOI：
10.1016/j.jnutbio.2004.10.010
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发表时间：
2005-03-01
影响因子：
5.6
通讯作者：
Park, JHY
中科院分区：
文献类型：
--
作者：
Kim, WK;Bang, MH;Park, JHY
在实验性结肠癌模型中，Quercetin具有化学保护作用，体外研究表明，Quercetin可以抑制HT-29结肠癌细胞的生长。ERBB2和ErbB3受体酪氨酸激酶与人类结肠癌的发生发展有关，并且这两种受体在HT-29细胞中高表达。在本研究中，我们研究了栎素对HT-29和SW480细胞凋亡的调节作用以及对ErbB2、ErbB3、Akt、Bax和Bcl2蛋白表达的影响。我们在不同浓度(0、25、50或100mU/L)的槲皮素或芦丁的存在下培养HT-29细胞。Quercetin以剂量依赖的方式抑制HT-29细胞的生长，而芦丁对细胞生长无影响。用50mU·m o-1/L的槲皮素处理的细胞，DNA呈现以细胞死亡为特征的橄榄核小体梯状条带。细胞裂解产物的Western印迹分析显示，在用槲皮素处理的细胞中，Bcl2水平呈剂量依赖性降低，而Bax则保持不变。Quercetin增加caspase-3裂解水平和聚(ADP-核糖)聚合酶的89 kDa片段。此外，25mU/L的槲皮素组细胞内磷酸化Akt水平显著降低，而总Akt水平仅在100mU/L组下降。此外，在栎素处理的细胞中还检测到ErbB2和ErbB3水平的剂量依赖性降低。用SW480细胞得到的结果与用HT-29细胞得到的结果相似。综上所述，我们的研究结果表明，栎素抑制结肠癌细胞的生长并诱导其凋亡，这可能是通过下调ErbB2/ErbB3信号和Akt通路的能力来实现的。(C)2005 Elsevier Inc.保留所有权利。
Quercetin has chemoprotective properties in experimental colon cancer models, and in vitro studies have demonstrated that quercetin inhibits HT-29 colon cancer cell growth. ErbB2 and ErbB3 receptor tyrosine kinases have been associated with the development of human colon cancer, and the expressions of both receptors are high in HT-29 cells. In this study, we assessed quercetin regulation of HT-29 and SW480 cell apoptosis and the influence of quercetin on the protein expression of ErbB2, ErbB3, Akt, Bax and Bcl-2. We cultured HT-29 cells in the presence of various concentrations (0, 25, 50, or 100 mu mol/L) of quercetin or rutin. Quercetin inhibited HT-29 cell growth in a dose-dependent manner, whereas rutin had no effect on the cell growth. DNA that was isolated from cells treated with 50 mu mol/L of quercetin exhibited an oliogonucleosomal laddering pattern characteristic of apoptotic cell death. Western blot analysis of cell lysates revealed that Bcl-2 levels decreased dose-dependently in cells treated with quercetin, but Bax remained unchanged. Quercetin increased levels of cleaved caspase-3 and the 89-kDa fragment of poly (ADP-ribose) polymerase. In addition, phosphorylated Akt levels were markedly lower in cells treated with 25 mu mol/L quercetin, but total Akt levels decreased only at 100 mu mol/L quercetin. Furthermore, a dose-dependent decrease in ErbB2 and ErbB3 levels was detected in quercetin-treated cells. The results obtained using SW480 cells were similar to those obtained with HT-29 cells. In conclusion, we have shown that quercetin inhibits cell growth and induces apoptosis in colon cancer cells, and that this may be mediated by its ability to down-regulate ErbB2/ErbB3 signaling and the Akt pathway. (c) 2005 Elsevier Inc. All rights reserved.