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酵母源重组燕麦蒽酰胺抑制结肠癌细胞的增殖、迁移和上皮间质转化。

Yeast-Derived Recombinant Avenanthramides Inhibit Proliferation, Migration and Epithelial Mesenchymal Transition of Colon Cancer Cells.

机构信息

Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.

CCM Italia research network (www.ccmitalia.unito.it), 10043 Torino, Italy.

出版信息

Nutrients. 2018 Aug 24;10(9):1159. doi: 10.3390/nu10091159.

DOI:10.3390/nu10091159
PMID:30149546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6165333/
Abstract

Avenanthramides (Avns), polyphenols found exclusively in oats, are emerging as promising therapeutic candidates for the treatment of several human diseases, including colon cancer. By engineering a strain, we previously produced two novel phenolic compounds, -()--coumaroyl-3-hydroxyanthranilic acid (Yeast avenanthramide I, YAvnI) and -()-caffeoyl-3-hydroxyanthranilic acid (Yeast avenanthramide II, YAvnII), which are endowed with a structural similarity to bioactive oat avenanthramides and stronger antioxidant properties. In this study, we evaluated the ability of these yeast-derived recombinant avenanthramides to inhibit major hallmarks of colon cancer cells, including sustained proliferation, migration and epithelial-mesenchymal transition (EMT). Using the human colon adenocarcinoma cell line HT29, we compared the impact of YAvns and natural Avns, including Avn-A and Avn-C, on colon cancer cells by performing MTT, clonogenic, adhesion, migration, and anchorage-independent growth assays, and analyzing the expression of EMT markers. We found that both YAvns and Avns were able to inhibit colon cancer cell growth by increasing the expression of p21, p27 and p53 proteins. However, YAvns resulted more effective than natural compounds in inhibiting cancer cell migration and reverting major molecular features of the EMT process, including the down-regulation of E-cadherin mRNA and protein levels.

摘要

燕麦素（Avns）是一种仅存在于燕麦中的多酚，作为治疗多种人类疾病（包括结肠癌）的有前途的治疗候选物，它正在崭露头角。通过工程化一株，我们之前生产了两种新型酚类化合物，-()--咖啡酰-3-羟基邻氨基苯甲酸（酵母燕麦素 I，YAvnI）和-()-阿魏酰-3-羟基邻氨基苯甲酸（酵母燕麦素 II，YAvnII），它们具有与生物活性燕麦素相似的结构和更强的抗氧化特性。在这项研究中，我们评估了这些酵母衍生的重组燕麦素抑制结肠癌细胞主要特征的能力，包括持续增殖、迁移和上皮-间充质转化（EMT）。使用人结肠腺癌细胞系 HT29，我们通过 MTT、集落形成、黏附、迁移和非锚定依赖性生长测定以及分析 EMT 标志物的表达，比较了 YAvns 和天然 Avns（包括 Avn-A 和 Avn-C）对结肠癌细胞的影响。我们发现 YAvns 和天然化合物都能够通过增加 p21、p27 和 p53 蛋白的表达来抑制结肠癌细胞的生长。然而，YAvns 在抑制癌细胞迁移和逆转 EMT 过程中的主要分子特征方面比天然化合物更有效，包括下调 E-钙黏蛋白 mRNA 和蛋白水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/efbea1e64a8d/nutrients-10-01159-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/50f1316ee5ac/nutrients-10-01159-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/a3822c221b51/nutrients-10-01159-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/eeafe324ec9b/nutrients-10-01159-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/dfe208bcd564/nutrients-10-01159-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/e8019e7500b7/nutrients-10-01159-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/754ce8301c10/nutrients-10-01159-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/efbea1e64a8d/nutrients-10-01159-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/50f1316ee5ac/nutrients-10-01159-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/a3822c221b51/nutrients-10-01159-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/eeafe324ec9b/nutrients-10-01159-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/dfe208bcd564/nutrients-10-01159-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/e8019e7500b7/nutrients-10-01159-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/754ce8301c10/nutrients-10-01159-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e95/6165333/efbea1e64a8d/nutrients-10-01159-g007.jpg

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Polyphenols in Colorectal Cancer: Current State of Knowledge including Clinical Trials and Molecular Mechanism of Action.结直肠癌中的多酚：包括临床试验和作用机制的分子方面的最新知识。
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Synthesis of avenanthramides using engineered Escherichia coli.
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