Stearoyl-CoA Desaturase-1 Enzyme Inhibition by Grape Skin Extracts Affects Membrane Fluidity in Human Colon Cancer Cell Lines

葡萄皮提取物抑制硬脂酰辅酶 A 去饱和酶 1 酶会影响人类结肠癌细胞系的膜流动性

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作者:Valeria Tutino, Isabella Gigante, Maria Principia Scavo, Maria Grazia Refolo, Valentina De Nunzio, Rosa Anna Milella, Maria Gabriella Caruso, Maria Notarnicola

Abstract

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.

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