[Anti-breast cancer effect of a mitochondrion-targeted derivative of ergosterol peroxide in vitro and in vivo].

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 µmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 µmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 µmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 µmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P<0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.

Populeuphrines A and B, two new cembrane diterpenoids from the resins of Populus euphratica.

Two new cembrane diterpenoids, named populeuphrines A and B (1 and 2), together with three known analogues (3-5) were isolated from the resins of Populus euphratica. The planar structures and relative configurations of 1 and 2 were elucidated by detailed 1 D and 2 D NMR spectroscopic analyses. The absolute configurations of 1 and 2 were determined by X-ray diffraction analysis and quantum chemical computation. Biological activities of all the isolates against proliferation of human cancer cells and umbilical cord mesenchymal stem cells were evaluated.