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Biochimica et biophysica acta

Studies on β-sitosterol and ceramide-induced alterations in the properties of cholesterol/sphingomyelin/ganglioside monolayers.


PMID 23838269

Abstract

Phytosterol-β-sitosterol promotes apoptosis in various cancer cells and inhibits their growth. Supplementation of cancer cells with this compound causes modifications in membrane composition, namely, substitution of cholesterol (Chol), decrease of sphingomyelin (SM) content and increase of ceramide (Cer) level. The aim of this work was to investigate the influence of partial replacement of cholesterol by plant sterol, substitution of sphingomyelin by ceramide and both these factors simultaneously on the properties of the monolayers composed of major lipids identified in breast cancer membranes, namely Chol/SM/GM3 mixtures. Brewster Angle Microcopy experiments and the analysis of the isotherms recorded during films compression and resulting parameters evidenced that β-sitosterol weakens the interactions between molecules, decreases films stability and condensation. The influence of ceramide on sterol/SM/GM3 films was reflected in strong modifications of their texture, however, the morphology of monolayer was determined by the structure of sterol present in the system. It was also found, that simultaneous replacement of 50mol% of Chol and SM by phytosterol and Cer, respectively, induces lipids segregation, which is manifested in large diversity of phases observed in BAM images. To facilitate the analysis of the data collected for multicomponent monolayers, the properties of selected sterol/GM3, sterol/Cer, SM/GM3, Cer/GM3 binary films were also investigated. The obtained results evidenced that the studied herein modifications in the composition of Chol/SM/GM3 monolayer, reflecting compositional alterations induced by phytosterol in cancer membranes, strongly affect the organization of model system, therefore they should be considered in the studies on anticancer mechanism of β-sitosterol.

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