Abstract
Flotillin-1 and flotillin-2 are highly conserved proteins that localize into cholesterol-rich microdomains in cellular membranes. Flotillins are closely related to the occurrence and development of various types of human cancers. Flotillin-1 is highly expressed in breast cancer, and the high expression level of flotillin-1 is significantly correlated with poorer patient survival. Here we studied the relationship between the formation of lipid rafts and the expression of flotillins and lipids in human breast cancer cells. We used the polyphenol compound resveratrol to alter the structure and function of the plasma membrane. Our data revealed an increase in fatty acids in MCF-7 and MDA-MB-231 cells upon resveratrol treatment. Interestingly, we also found an increase in the expression of both flotillin-1 and flotillin-2 in breast tumor cells after treatment. Resveratrol also induced changes in the pattern of flotillin distribution among detergent-resistant lipid rafts fractions in both cell lines and induced the nuclear translocation of flotillin-2. Since resveratrol has been pointed out as a putative cancer therapy agent, our results could have an impact on the understanding of the effects of resveratrol in tumor cells.
Highlights
Lipid rafts are specialized membrane structures that are involved in myriad of cellular functions, such as endocytosis, cell signaling and the control of cell survival and death
We investigated the effects of resveratrol treatment on the viability, using the MTT assay, of two human breast tumor cells (MCF-7 and MDA-MB-231) and in the non-tumor mouse breast epithelial cell line 4T1
We found that resveratrol induced: (I) a cytotoxic effect in a dose-dependent manner; (ii) an increase in the expression of flotillin-1 and -2; (iii) an increase in the total amount of fatty acids; and (iv) a redistribution of flotillin-1 from the cytosol and plasma membrane to lipid raft microdomains and the nuclear translocation of flotillin-2
Summary
Lipid rafts are specialized membrane structures that are involved in myriad of cellular functions, such as endocytosis, cell signaling and the control of cell survival and death They are enriched in cholesterol, sphingolipids and specific proteins, such as flotillins. Colin and colleagues showed a different interaction of resveratrol and the plasma membrane in cancer cells, where resveratrol could enter the cell by endocytosis via lipid rafts activating downstream signaling pathways[11]. In face of the recent findings related to the influence of resveratrol in the organization of the plasma membrane, and the lipid rafts, we decided to study the effects of resveratrol in the expression of flotillins and lipids in human breast cancer cells
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