Bacterial Natural Disaccharide (Trehalose Tetraester): Molecular Modeling and in Vitro Study of Anticancer Activity on Breast Cancer Cells

Isolation and characterization of new biologically active substances affecting cancer cells is an important issue of fundamental research in biomedicine. Trehalose lipid was isolated from Rhodococcus wratislaviensis strain and purified by liquid chromatography. The effect of trehalose lipid on cell viability and migration, together with colony forming assays, were performed on two breast cancer (MCF7—low metastatic; MDA-MB231—high metastatic) and one “normal” (MCF10A) cell lines. Molecular modeling that details the structure of the neutral and anionic form (more stable at physiological pH) of the tetraester was carried out. The tentative sizes of the hydrophilic (7.5 Å) and hydrophobic (12.5 Å) portions of the molecule were also determined. Thus, the used trehalose lipid is supposed to interact as a single molecule. The changes in morphology, adhesion, viability, migration, and the possibility of forming colonies in cancer cell lines induced after treatment with trehalose lipid were found to be dose and time dependent. Based on the theoretical calculations, a possible mechanism of action and membrane asymmetry between outer and inner monolayers of the bilayer resulting in endosome formation were suggested. Initial data suggest a mechanism of antitumor activity of the purified trehalose lipid and its potential for biomedical application.

Soluble Sugar and Lipid Readjustments in the Yarrowia lipolytica Yeast at Various Temperatures and pH

Microorganisms cope with a wide range of environmental challenges using different mechanisms. Their ability to prosper at extreme ambient pH and high temperatures has been well reported, but the adaptation mechanism often remains unrevealed. In this study, we addressed the dynamics of lipid and sugar profiles upon different cultivation conditions. The results showed that the cells grown at various pH and optimal temperature contained mannitol as the major cytosol sugar alcohol. The elevated temperature of 38 °C led to a two- to three-fold increase in total cytosol sugars with concurrent substitution of mannitol for trehalose. Lipid composition in the cells at optimal temperature changed insignificantly at any pH tested. The increase in the temperature caused some drop in the storage and membrane lipid levels, remarkable changes in their composition, and the degree of unsaturated fatty acids. It was shown that the fatty acid composition of some membrane phospholipids varied considerably at changing pH and temperature values. The data showed a pivotal role and flexibility of the sugar and lipid composition of Y. lipolytica W29 in adaptation to unfavorable environmental conditions.