A Potent Anticancer Agent of Shikonin Derivative Targeting Tubulin

In this study, a shikonin ester derivative, compound 3g , was selected to evaluate its anticancer activities and we found that compound 3g exhibited better antitubulin activities against the human HepG2 cell line with an IC₅₀ value of 1.097 μM. Furthermore, the inhibition of tubulin polymerization results indicated that compound 3g demonstrated the most potent antitubulin activity (IC₅₀ = 13.88), which was compared with shikonin and colchicine as positive controls (IC₅₀ = 25.28 μM and 22.56 μM), respectively. Compound 3g was simulated to have good binding site with tubulin and arrested the cell cycle at G2/M phase, which also induces apoptosis in HepG2 cells, in which P53 and members of Bcl‐2 protein family were both involved in the progress of apoptosis revealed by western blot. Confocal microscopy observations revealed compound 3g targeted tubulin and altered its polymerization by interfering with microtubule organization. Based on these results, compound 3g functions as a potent anticancer agent targeting tubulin. Chirality 27:274–280, 2015.. © 2015 Wiley Periodicals, Inc.     

Geographic distribution and migration pathways of Pistacia – present,past and future

The global distribution of Pistacia is correlated to its adaptability to environmental conditions and mechanisms that had driven the genus to the current unique narrow latitudinal belt in between 10° North and 45° North. The current geostatisitcal distribution maps of the genus are shown and the derived probability maps over a period between 121 Kyr before present and the year 2100 were calculated. The tolerance of Pistacia trees to harsh climate conditions was related to leaf phenology, evergreeness vs deciduousness, which has led to geographic classification of the genus in two corresponding sections that corroborate recent molecular genetic studies. The deciduous trees are more tolerant to extreme climate conditions (?26°C to 46°C) than the evergreen species (?8°C to 41°C), except Pistacia lentiscus, which occurs at a max. temperature of 45°C. The close spatial distribution of the later species and the deciduous ones may have been conducive in further evolution of the genus. Based on the long evolution of Pistacia (approx. 84 Ma), we suggested that the genus may have originated in the boreal forest and its migration pathways might have been evoked in relation to climate change, shifting the species distribution to evolving suitable environmental conditions. The fact that most of the genera in the family of Anacardiaceae and the whole genus Pistacia are dioecious raised questions about plausible relationships between the geographic distribution, environmental conditions and evolution of dioecy. The genus Pistacia was shown to be a good candidate for research about the relationships between environmental conditions, adaptation traits and geographic distribution.     

Effects of geographical heterogeneity in species interactions on the evolution of venom genes

Geographical heterogeneity in the composition of biotic interactions can create a mosaic of selection regimes that may drive the differentiation of phenotypes that operate at the interface of these interactions. Nonetheless, little is known about effects of these geographical mosaics on the evolution of genes encoding traits associated with species interactions. Predatory marine snails of the family Conidae use venom, a cocktail of conotoxins, to capture prey. We characterized patterns of geographical variation at five conotoxin genes of a vermivorous species, Conus ebraeus, at Hawaii, Guam and American Samoa, and evaluated how these patterns of variation are associated with geographical heterogeneity in prey utilization. All populations show distinct patterns of prey utilization. Three ‘highly polymorphic’ conotoxin genes showed significant geographical differences in allelic frequency, and appear to be affected by different modes of selection among populations. Two genes exhibited low levels of diversity and a general lack of differentiation among populations. Levels of diversity of ‘highly polymorphic’ genes exhibit a positive relationship with dietary breadth. The different patterns of evolution exhibited by conotoxin genes suggest that these genes play different roles in prey capture, and that some genes are more greatly affected by differences in predator–prey interactions than others. Moreover, differences in dietary breadth appear to have a greater influence on the differentiation of venoms than differences in the species of prey.