Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Italy.
Personalized Medicine Laboratory, National Institute of Gastroenterology "S. de Bellis" Research Hospital, 70013 Castellana Grotte, Italy.
Nutrients. 2020 Mar 4;12(3):693. doi: 10.3390/nu12030693.
The polyphenolic compounds present in grape extracts have chemopreventive and anticancer properties. Here, we studied the ability of two grape skin extracts (GSEs), Autumn Royal and Egnatia, to influence the cell motility and membrane fluidity regulated by the enzyme Stearoyl-CoA desaturase-1 (SCD1) which increases with the cancer aggressiveness. Caco2 and SW480 human colon cancer cell lines were treated with increasing concentrations of GSEs to evaluate cell proliferation and motility. SCD1 levels were evaluated in both treated cell lines, by membrane lipidomic analysis conducted by gas chromatography. The expression levels of SCD1 and other factors involved in the reorganization of the cytoskeleton and focal adhesions were assessed by Real-time PCR, Western Blotting, and Immunofluorescence staining. High-performance liquid chromatography (HPLC) analyses were performed to determine the phenolic composition in the GSEs, finding them more expressed in Autumn Royal than in Egnatia. Both treatments reduced the levels of SCD1, phospho-Rac1/Cdc42/Rac1/Cdc42 ratio, Cofilin, Vimentin, and phospho-Paxillin especially in Caco2 compared to SW480, showing a different behavior of the two cell lines to these natural compounds. Our findings show that GSEs block the cell migration and membrane fluidity through a new mechanism of action involving structural cellular components.
葡萄提取物中的多酚化合物具有化学预防和抗癌特性。在这里，我们研究了两种葡萄皮提取物（GSE），即 Autumn Royal 和 Egnatia，影响由 Stearoyl-CoA desaturase-1（SCD1）调节的细胞迁移和膜流动性的能力，SCD1 的活性随着癌症侵袭性的增加而增加。用不同浓度的 GSE 处理 Caco2 和 SW480 人结肠癌细胞系，以评估细胞增殖和迁移。通过气相色谱法进行膜脂质组学分析，评估了两种处理细胞系中的 SCD1 水平。通过实时 PCR、Western Blotting 和免疫荧光染色评估 SCD1 和参与细胞骨架和焦点粘连重排的其他因子的表达水平。进行高效液相色谱（HPLC）分析以确定 GSE 中的酚类成分，发现 Autumn Royal 中的含量高于 Egnatia。两种处理均降低了 SCD1、磷酸化 Rac1/Cdc42/Rac1/Cdc42 比值、Cofilin、波形蛋白和磷酸化 Paxillin 的水平，尤其是在 Caco2 中与 SW480 相比，这两种细胞系对这些天然化合物表现出不同的行为。我们的研究结果表明，GSE 通过一种新的作用机制阻断细胞迁移和膜流动性，该机制涉及结构细胞成分。
