β-Asarone Inhibits Invasion and EMT in Human Glioma U251 Cells by Suppressing Splicing Factor HnRNP A2/B1

β-asarone, the main component in the volatile oil of Acori tatarinowii Rhizoma, has been found to possess antitumor activity. However, its effect and mechanisms against tumor invasion and epithelial–mesenchymal transition (EMT) are still unclear. In this study, no or less cytotoxicity was caused by β-asarone within 0–120 μM in human glioma U251 cells for 48 h. β-asarone (30 and 60 μM) inhibited the migration of U251 cells in the wound healing assay, suppressed the invasion of U251 cells in the Boyden chamber invasion assay, and inhibited the adhesion of U251 cells onto the Matrigel. Moreover, β-asarone suppressed EMT with the up-regulation of E-cadherin and the down-regulation of vimentin. HnRNP A2/B1, a well-characterized oncogenic protein, was shown at a high basal level in U251 cells and β-asarone reduced hnRNP A2/B1 expression in a concentration and time-dependent way. Importantly, hnRNP A2/B1 overexpression significantly counteracted the inhibition of β-asarone on the migration, invasion, and adhesion of U251 cells and reversed the modulation of EMT markers by β-asarone. Additionally, β-asarone decreased the MMP-9 and p-STAT3 in U251 cells, which was also reversed by hnRNP A2/B1 overexpression. Together, our results suggest that hnRNP A2/B1 may be a potential molecular target underlying the inhibitory effect of β-asarone on invasion and EMT in glioma cells

β-Asarone Induces Apoptosis and Cell Cycle Arrest of Human Glioma U251 Cells via Suppression of HnRNP A2/B1-Mediated Pathway In Vitro and In Vivo

HnRNP A2/B1 has been found to be an oncogenic protein strongly related to the growth of human glioma cells. Herein, β-asarone, the main component in the volatile oil of Acori tatarinowii Rhizoma, inhibited the cell viability, proliferation, and colony formation ability of U251 cells. Moreover, β-asarone induced apoptosis and cell cycle arrest at the G1 phase. Notably, β-asarone suppressed the expression of hnRNP A2/B1 and hnRNPA2/B1 overexpression remarkably reversed β-asarone-mediated apoptosis and cell cycle arrest. Importantly, β-asarone promoted the alternative splicing of Bcl-x by enhancing the ratio of Bcl-xS/Bcl-xL. Meanwhile, hnRNPA2/B1 overexpression mitigated the promoting effect of β-asarone on the alternative splicing of Bcl-x. β-asarone also regulated the level of the key proteins involved in the death receptor pathway and mitochondrial apoptosis pathway. Additionally, β-asarone modulated the cell cycle-related proteins p21, p27, Cdc25A, cyclin D, cyclin E, and CDK2. Finally, β-asarone inhibited tumor growth and induced apoptosis in nude mice bearing U251 tumor xenografts. β-asarone also suppressed the hnRNP A2/B1 expression, enhanced the expression of cleaved-caspase 3 and p27 and the ratio of Bcl-xS/Bcl-xL, and reduced the expression of CDK2 in U251 xenografts. Together, β-asarone-induced apoptosis and cell cycle arrest of U251 cells may be related to the suppression of hnRNPA2/B1-mediated signaling pathway

Experimental confirmation of driving pressure boosting and smoothing for hybrid-drive inertial fusion at the 100-kJ laser facility

Abstract In laser-driven inertial confinement fusion, driving pressure boosting and smoothing are major challenges. A proposed hybrid-drive (HD) scheme can offer such ideal HD pressure performing stable implosion and nonstagnation ignition. Here we report that in the hemispherical and planar ablator targets installed in the semicylindrical hohlraum scaled down from the spherical hohlraum of the designed ignition target, under indirect-drive (ID) laser energies of ~43–50 kJ, the peak radiation temperature of 200 ± 6 eV is achieved. And using only direct-drive (DD) laser energies of 3.6–4.0 kJ at an intensity of 1.8 × 1015 W/cm2, in the hemispherical and planar targets the boosted HD pressures reach 3.8–4.0 and 3.5–3.6 times the radiation ablation pressure respectively. In all the above experiments, significant HD pressure smoothing and the important phenomenon of how a symmetric strong HD shock suppresses the asymmetric ID shock pre-compressed fuel are demonstrated. The backscattering and hot-electron energy fractions both of which are about one-third of that in the DD scheme are also measured