Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4.
Cyanidin-3-O-glucoside inhibits epithelial-to-mesenchymal transition, and migration and invasion of breast cancer cells by upregulating KLF4.
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Cyanidin-3-O-glucoside 通过上调 KLF4 抑制乳腺癌细胞上皮间质转化以及迁移和侵袭
DOI：
10.29219/fnr.v64.4240
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发表时间：
2020
影响因子：
3.3
通讯作者：
Hu Z
中科院分区：
文献类型：
--
作者：
Chen D;Yuan M;Ye Q;Wang X;Xu J;Shi G;Hu Z
花青素（Anthocyanins，ACNs）具有抑制乳腺癌生长的作用，但其对乳腺癌细胞上皮间质转化（EMT）、细胞迁移和侵袭的影响及其机制的研究还很有限。对这些性质的全面了解可能会提供有关如何使用这些天然化合物预防和治疗癌症的有用信息。这项工作的目的是研究花青素-3-O-葡萄糖苷（Cy 3G），在可食用水果中分布最广泛的ACN之一，在EMT过程中的作用，以及乳腺癌细胞的细胞迁移和侵袭，以及Cy 3G如何在这些细胞中建立这些功能作用的潜在分子机制。用Cy 3G（20 μM）处理MDA-MB-231和MDA-MB-468乳腺癌细胞24小时，然后将细胞用于细胞迁移和侵袭测定。采用Western blotting、荧光素酶法、泛素化法、基因敲除法和放线菌酮追踪法分析Cy 3G抑制EMT、细胞迁移和侵袭的分子机制。Cy 3G通过上调Krüppel样因子4（KLF 4）蛋白表达，抑制乳腺癌细胞的EMT过程，并显著抑制乳腺癌细胞的迁移和侵袭（P ≤ 0. 05）。在MDA-MB-231细胞中，KLF 4敲除未显示Cy 3G处理后EMT标志物表达以及细胞迁移和侵袭的任何变化（P ≥ 0.05），这强烈表明Cy 3G的作用是由KLF 4介导的。此外，我们确定Cy 3G通过下调FBXO 32（KLF 4的E3连接酶）间接上调KLF 4表达。Cy 3G是一种潜在的抗癌试剂，因为它可以通过上调KLF 4来抑制EMT和乳腺癌细胞的迁移和侵袭。
Anthocyanins (ACNs) are capable of suppressing breast cancer growth; however, investigation on the effect and mechanism of ACNs on epithelial-to-mesenchymal transition (EMT), and cell migration and invasion in breast cancer cells is limited. A complete understanding of those properties may provide useful information on of how to use these natural compounds for cancer prevention and treatment. The aim of this work was to investigate the role of cyanidin-3-O-glucoside (Cy3G), one of the most widely distributed ACNs in edible fruits, in the EMT process, and cell migration and invasion of breast cancer cells, and its underlying molecular mechanisms of how Cy3G establishes these functional roles in these cells. MDA-MB-231 and MDA-MB-468 breast cancer cells were treated with Cy3G (20 μM) for 24 h, and then the cells were used for cell migration and invasion assay. Western blotting, luciferase assay, ubiquitination assay, gene knockdown, and cycloheximide chase assay were performed to analyze the molecular mechanisms of Cy3G in suppressing EMT, and cell migration and invasion. Cy3G inhibited the EMT process in these cells and significantly suppressed the migration and invasion of breast cancer cells (P ≤ 0.05) by upregulating Krüppel-like factor 4 (KLF4) expression at protein level. KLF4 knockdown in MDA-MB-231 cells did not reveal any change in EMT marker expression, and cell migration and invasion upon treatment with Cy3G (P ≥ 0.05), which strongly indicated that the effects of Cy3G were mediated by KLF4. Furthermore, we determined that Cy3G indirectly upregulated KLF4 expression by downregulating FBXO32, which is the E3 ligase of KLF4. Cy3G is a potential anticancer reagent as it can inhibit EMT and breast cancer cell migration and invasion by upregulating KLF4.
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