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.

The thermosensitivity of delayed fluorescence, the relative values of variable chlorophyll fluorescence and the degree of quenching of 9-aminoacridine fluorescene were studied in the chloroplasts from heat-acclimated and non-acclimated (treated 6 h at 52,5°C) young bean plants. The temperature sensitivity of each parameter studied was defined by that temperature at which chloroplast activity decreased by 50% (T50) of its maximum value. There was appreciable increase in the thermostability of membrane energization in chloroplasts isolated from acclimated and non-acclimated plants compared with the controls. The photosynthetic parameters differed according to the suspending medium and the preacclimation treatment. When chloroplast were suspended in phosphate buffer with the addition of stabilizing compounds (2 M sucrose or 0.5% human serum albumin) the thermostability of the thylakoid membranes increased, as was evident by the increases in T50 of about 8-10° C (sucrose) and 2-5° C (human serum albumin) for all the parameters investigated. Photoinduced quenching of 9-aminoacridine fluorescence decreased to some extent in the presence of protective compounds, but in chloroplasts from acclimated plants the T50 was practically equal to that for their long-lived luminescence under the same conditions. At the thylakoid membrane level, acclimation was clearly manifested as an increased thermostability of photoinduced proton-gradient formation.

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The influence of mono- (K(+)) and divalent (Mg(2+)) cations and protons (pH) on the temperature sensitivity of thylakoid membranes was investigated in three groups of young bean plants (control, heat-acclimated and non-acclimated). Thylakoid-membrane function was monitored by second and millisecond delayed fluorescence and 9-aminoacridine fluorescence quenching. It was established that metal ions at investigated concentrations decreased the thermostability of the photosynthetic parameters - an increase of MgSO4 concentration from 0.1 to 20 mM decreased the temperature of their half-inactivation (T50) by 13°C. At the same time the pH dependence of the thermal stability of these parameters showed a maximum at pH 5.5-6.5. The half-inactivation temperatures of those photosynthetic parameters connected with the ability of the thylakoid membrane to form light-induced proton gradients increased by 6-7°C in the heat-acclimated plants compared with the control. It was assumed that the temperature inactivation of photosynthetic electron transfer and the energization of the thylakoid membrane was determined both by the thermoinduced dissociation of the light-harvesting chlorophyll a/b protein complex from PSII, leading to destruction of the excitation energy transfer to the reaction centres, and by the thermal denaturation of the membrane-protein components. The rate of these processes was probably controlled by the size of the negative surface charge and the viscosity of the thylakoid membrane.

In this study, we present initial data for the potential anti-cancer effects of standardized Bulgarian Petasites hybridus root extract against breast cancer cells. The results showed that Butterbur extract (BE) caused a dose-dependent selective reduction in viability with concomitant increase of apoptosis in human breast cancer cells after 72 h treatment. We found the highest cytotoxicity of BE to MDA-MB-231 cells (IC 50 -520 μg/mL), followed by the MCF-7 cancer cell line (IC 50 -865 μg/mL). At the same time, the extract exhibited very low cytotoxicity to the non-tumorigenic L929 cell line (two-fold higher inhibitory concentration -1252 μg/mL). As a result of our experiments we made the conclusion that Butterbur root extract shows selective high cytotoxicity and nucleus alterations in cancer cells comparing to non-cancerous cells.

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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 which has not been sufficiently characterized. 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 techniques (i.e., scanning fluorescence correlation spectroscopy, line-scan fluorescence correlation spectroscopy and generalized polarization imaging) 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 might be linked to its effects on fundamental biophysical properties of lipid membranes in cancer cells.