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

Polymers

Severina Semkova¹  Biliana Nikolova¹  Iana Tsoneva¹  Georgi Antov¹  Silvia Angelova²  Ivanka Stoineva³  Proletina Kardaleva³  Juliana Ivanova⁴  Ivanina Vasileva⁴  Lilyana Nacheva⁵  Nelly Christova⁵  Lyudmila Kabaivanova⁵ 

[1] Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria;Institute of Optical Materials and Technologies “Acad. Jordan Malinowski”, Bulgarian Academy of Sciences, Sofia, “Acad. G. Bonchev” Str., Bl. 109, 1113 Sofia, Bulgaria;Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., Bl. 9, 1113 Sofia, Bulgaria;Institute of Plant Physiology and Genetics Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., Bl. 21, 1113 Sofia, Bulgaria;The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., Bl. 26, 1113 Sofia, Bulgaria;

关键词: bacterial natural disaccharide;    trehalose tetraester;    rhodococcus wratislaviensis;    breast cancer;    anticancer activity;    molecular modeling;   

DOI  :  10.3390/polym12020499

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown