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.
Highlights
Metastasis is an active process in which cancer cells are able to move through the extracellular matrix (ECM) barriers thanks to local proteolysis, physical movement, lamellipodia, and filopodia formation.Some motility factors can contribute to the progression of metastases and to the increase of invasiveness by inducing rearrangements of the cytoskeleton, adaptations in cell adhesion, and stimulating epithelial to mesenchymal transition (ETM) [1,2,3].Nutrients 2020, 12, 693; doi:10.3390/nu12030693 www.mdpi.com/journal/nutrientsconformational cellular changes can be influenced both by a series of complex signaling pathways and by changes in the lipid profile of the plasma membrane
Elevated levels of Stearoyl-CoA desaturase-1 (SCD1) and of monounsaturated fatty acids (MUFAs) in the lipid bilayer membranes have been detected in several tumors, such as colorectal cancer (CRC), and high levels of SCD1 have been positively related to the aggressiveness and malignancy of the disease [6,14,15]
Both total phenolic content (TPC) and anthocyanins, flavonols and flavanols were significantly higher in Autumn Royal than in Egnatia
Summary
Metastasis is an active process in which cancer cells are able to move through the extracellular matrix (ECM) barriers thanks to local proteolysis, physical movement, lamellipodia, and filopodia formation.Some motility factors can contribute to the progression of metastases and to the increase of invasiveness by inducing rearrangements of the cytoskeleton, adaptations in cell adhesion, and stimulating epithelial to mesenchymal transition (ETM) [1,2,3].Nutrients 2020, 12, 693; doi:10.3390/nu12030693 www.mdpi.com/journal/nutrientsconformational cellular changes can be influenced both by a series of complex signaling pathways and by changes in the lipid profile of the plasma membrane. Lipids are a group of compounds that influence different cellular functions, including cell membrane fluidity and cell morphology [4,5,6]. Stearoyl-CoA desaturase-1 (SCD1) is a key lipogenic enzyme that converts saturated fatty acids (SFAs), such as palmitic acid (C16:0) and stearic acid (C18:0), into monounsaturated fatty acids (MUFAs), such as palmitoleic acid (16:1n-7) and oleic acid (C18:1n-9). SCD1 activity can be estimated from the desaturation indices given by the palmitoleic acid/palmitic acid and oleic acid/stearic acid ratios [11,12]. The lipids derived from the unsaturation carried out by SCD1, are used to modulate membrane structure and fluidity; an important role of SCD1 in cell proliferation has been hypothesized [6,13]. Elevated levels of SCD1 and of MUFAs in the lipid bilayer membranes have been detected in several tumors, such as colorectal cancer (CRC), and high levels of SCD1 have been positively related to the aggressiveness and malignancy of the disease [6,14,15]
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