Nikolova Biliana, Antov Georgi, Semkova Severina, Tsoneva Iana, Christova Nelly, Nacheva Lilyana, Kardaleva Proletina, Angelova Silvia, Stoineva Ivanka, Ivanova Juliana, Vasileva Ivanina, Kabaivanova Lyudmila
Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, "Acad. G. Bonchev" Str., Bl. 21, 1113 Sofia, Bulgaria.
Institute of Plant Physiology and Genetics Bulgarian Academy of Sciences, "Acad. G. Bonchev" Str., Bl. 21, 1113 Sofia, Bulgaria.
Polymers (Basel). 2020 Feb 24;12(2):499. doi: 10.3390/polym12020499.
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 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.
分离和鉴定影响癌细胞的新型生物活性物质是生物医学基础研究的一个重要问题。从菌株中分离出海藻糖脂，并通过液相色谱法进行纯化。对两种乳腺癌细胞系（MCF7 - 低转移性；MDA - MB231 - 高转移性）和一种“正常”细胞系（MCF10A）进行了海藻糖脂对细胞活力和迁移的影响以及集落形成测定。对四酯的中性和阴离子形式（在生理pH下更稳定）的结构进行了详细的分子建模。还确定了分子亲水性部分（7.5 Å）和疏水性部分（12.5 Å）的暂定尺寸。因此，所使用的海藻糖脂被认为以单分子形式相互作用。发现用海藻糖脂处理后诱导的癌细胞系中形态、黏附、活力、迁移以及形成集落的可能性变化与剂量和时间有关。基于理论计算，提出了一种可能的作用机制以及双层膜外层和内层单分子层之间导致内体形成的膜不对称性。初步数据表明了纯化的海藻糖脂的抗肿瘤活性机制及其在生物医学应用中的潜力。
