Sphingosine­1­phosphate analogue FTY720 exhibits a potent anti­proliferative effect on glioblastoma cells.

Sphingosine­1­phosphate (S1P) plays a key role in cell survival, growth, migration, and in angiogenesis. In glioma, it triggers the activity of the S1P­receptor 1 and of the sphingosine kinase 1; thus influencing the survival rate of patients. The aim of the present study was to investigate the anti­proliferative effect of the S1P analogue FTY720 (fingolimod) in glioblastoma (GBM) cells. A172, G28, and U87 cells were incubated with micromolar concentrations of FTY720 or temozolomide (TMZ) for 24 to 72 h. Proliferation and half maximal inhibitory concentration (IC50) were determined by using the xCELLigence system. FACS analysis was performed to check the cell cycle distribution of the cells after a 72­h incubation with FTY720. This was then compared to TMZ­incubated and to untreated cells. Gene expression was detected by RT­qPCR in A172, G28, U87 and three primary GBM­derived cell lines. FTY720 was able to reduce the number of viable cells. The IC50 value was 4.6 µM in A172 cells, 17.3 µM in G28 cells, and 25.2 µM in U87 cells. FTY720 caused a significant arrest of the cell cycle in all cells and stabilized or over­expressed the level of AKT1, MAPK1, PKCE, RAC1, and ROCK1 transcripts. The TP53 transcript level remained stable or was downregulated after treatment with FTY720. FTY720 may be a promising target drug for the treatment of GBM, as it has a strong anti­proliferative effect on GBM cells.

Observation of relativistic E x e vibronic coupling in Rb3 and K3 quartet states on helium droplets.

Spectroscopy of alkali-metal complexes on helium droplets (He(N), N=1000-10 000) provides the unique opportunity to observe high-spin species, which exhibit prominent spin-orbit (SO) effects. In this work we present laser-induced-fluorescence and magnetic-circular-dichroism (MCD) spectra of the (2)(4)E(')<--(1)(4)A(2) (') band of Rb(3) and K(3) on He(N). For Rb(3) we find a progression of four SO split bands, weakly perturbed by linear vibronic [Jahn-Teller (JT)] coupling. The K(3) transition was previously observed and interpreted in terms of linear and quadratic JT effects in the (2)(4)E(') state [J. H. Reho et al., J. Chem. Phys. 115, 10265 (2001)]. The structure of the MCD spectrum, however, clearly reveals the importance of SO coupling also for the K(3) transition and suggests a different assignment with weak linear JT and nonsignificant quadratic JT coupling. The observed strong C-type MCD spectra arise from different populations of the ground-state Zeeman sublevels. Thus a quantitative analysis allows a determination of the spin temperature, and since alkali-metal complexes are situated on the surface of the helium droplet this corresponds to a determination of the surface temperature. Our results from the trimer spectra are consistent with the value of approximately 0.4 K, which is found in the interior of a droplet and which we already confirmed for the surface from the spectra of triplet-state alkali-metal dimers in a previous work.