Effect of Erufosine on Membrane Lipid Order in Breast Cancer Cell Models.

Alkylphospholipids are a novel class of antineoplastic drugs showing remarkable therapeutic potential. Among them, erufosine (EPC3) is a promising drug for the treatment of several types of tumors. While EPC3 is supposed to exert its function by interacting with lipid membranes, the exact molecular mechanisms involved are not known yet. In this work, we applied a combination of several fluorescence microscopy and analytical chemistry approaches (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy, generalized polarization imaging, as well as thin layer and gas chromatography) to quantify the effect of EPC3 in biophysical models of the plasma membrane, as well as in cancer cell lines. Our results indicate that EPC3 affects lipid-lipid interactions in cellular membranes by decreasing lipid packing and increasing membrane disorder and fluidity. As a consequence of these alterations in the lateral organization of lipid bilayers, the diffusive dynamics of membrane proteins are also significantly increased. Taken together, these findings suggest that the mechanism of action of EPC3 could be linked to its effects on fundamental biophysical properties of lipid membranes, as well as on lipid metabolism in cancer cells.

Dimethylsphingosine and miltefosine induce apoptosis in lung adenocarcinoma A549 cells in a synergistic manner.

Lung cancer is one of the most common and lethal types of oncological diseases. Despite the advanced therapeutic approaches, the prognosis for lung cancer still remains poor. Apparently, there is an imperative need for more efficient therapeutic strategies. In this work we report that concurrent treatment of human adenocarcinoma A549 cells with specific concentrations of two antitumor agents, the sphingosine kinase 1 inhibitor N, N dimethylsphingosine (DMS) and the alkylphosphocholine miltefosine, induced synergistic cytotoxic effect, which was confirmed by calculation of the combination index. The simultaneous action of these agents, induced significant decrease of A549 cell number, as well as pronounced morphological alterations. Combined drugs caused substantial apoptotic events, and significant reduction of the pro-survival marker sphingosine- 1-phosphate (S1P), when compared to the individual treatments with each of the anticancer drugs alone. Miltefosine is known to affect the synthesis of choline-containing phospholipids, including sphingomyelin, but we report for the first time that it also reduces S1P. Here we suggest a putative mechanism underlying the effect of miltefosine on sphingosine kinase 1, involving miltefosine-induced inhibition of protein kinase C. In conclusion, our findings provide a possibility for treatment of lung cancer cells with lower concentrations of the two antitumor drugs, DMS and miltefosine, which is favorable, regarding their potential cytotoxicity to normal cells.

Study of potential biomedical application of sol-gel derived Zn-doped SiO2-hydroxypropyl cellulose nanohybrids.

A series of Zn-doped hybrid materials based on silica from tetraethoxysilane (TEOS) and hydroxypropyl cellulose (HPC) were prepared by a sol-gel route. The structure, morphology and thermal behavior of synthesized hybrids were characterized by infrared (IR) spectroscopy, ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM) and differential thermal analysis with thermogravimetric analysis (DTA/TG). The obtained materials were investigated for a potential biomedical application. The antibacterial properties of hybrids were investigated by measuring the inhibition zones formed around the materials containing different zinc content in presence of reference strains of Gram-positive and Gram-negative bacteria. The biocompatibility tests showed no cytotoxicity and genotoxicity, as well as no changes in actin cytoskeleton organization for hybrids with Zn content below 5 wt%.

New cycloartane triterpenes from bioactive extract of propolis from Pitcairn Island.

Dichloromethane extract of propolis (DCME) originating from Pitcairn Island demonstrated potent cytotoxicity against triple-negative MDA-MB-231 human breast carcinoma cells. The results from MTT assay showed that DCME inhibits the growth of the cancer cells in a dose- and time-dependent manner and upon the cell growth inhibition propolis extract provoked apoptotic changes in the cell nuclei. A detailed chemical investigation of DCME led to the isolation of four new cycloartane triterpenes (1-4), along with 17 known compounds (5-21). The structures of the new compounds were elucidated by means of extensive analysis of their spectroscopic data and comparison with those reported for their analogues. In vitro antimicrobial activity of new compounds (1-4) along with the DCME against four human pathogens was evaluated. All tested constituents except compound 2 were highly active against Escherichia coli with MIC 64 µg/ml. Compound 1 exhibited high antifungal activity against Candida albicans with potency close to that of the positive control (amphotericin B). The DCME showed very good antimicrobial activity against Staphylococcus aureus, Escherichia coli and Candida albicans. This is the first study on propolis from Pitcairn Island.