SSPH I, A Novel Anti-cancer Saponin, Inhibits EMT and Invasion and Migration of NSCLC by Suppressing MAPK/ERK1/2 and PI3K/AKT/mTOR Signaling Pathways.

BACKGROUND: Saponin of Schizocapsa plantaginea Hance I (SSPH I)，a bioactive saponin found in Schizocapsa plantaginea, exhibits significant anti-proliferation and antimetastasis in lung cancer. OBJECTIVE: To explore the anti-metastatic effects of SSPH I on non-small cell lung cancer (NSCLC) with emphasis on epithelial-mesenchymal transition (EMT) both in vitro and vivo. METHODS: The effects of SSPH I at the concentrations of 0, 0.875,1.75, and 3.5 µM on A549 and PC9 lung cancer cells were evaluated using colony formation assay, CCK-8 assay, transwell assay and wound-healing assay. The actin cytoskeleton reorganization of PC9 and A549 cells was detected using the FITC-phalloidin fluorescence staining assay. The proteins related to EMT (N-cadherin, E-cadherin and vimentin), p- PI3K, p- AKT, p- mTOR and p- ERK1/2 were detected by Western blotting. A mouse model of lung cancer metastasis was established by utilizing 95-D cells, and the mice were treated with SSPH I by gavage. RESULTS: The results suggested that SSPH I significantly inhibited the migration and invasion of NSCLC cells under a non-cytotoxic concentration. Furthermore, SSPH I at a non-toxic concentration of 0.875 µM inhibited F-actin cytoskeleton organization. Importantly, attenuation of EMT was observed in A549 cells with upregulation in the expression of epithelial cell marker E-cadherin and downregulation of the mesenchymal cell markers vimentin as well as Ncadherin. Mechanistic studies revealed that SSPH I inhibited MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways. CONCLUSION: SSPH I inhibited EMT, migration, and invasion of NSCLC cells by suppressing MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways, suggesting that the natural compound SSPH I could be used for inhibiting metastasis of NSCLC.

In situ generation and efficient activation of H2O2 for pollutant degradation over CoMoS2 nanosphere-embedded rGO nanosheets and its interfacial reaction mechanism.

Consumption of additional H2O2 is necessary in classical Fenton catalysis. Herein, we report a novel and special nanocatalyst consisting of CoMoS2 nanosphere-embedded, reduced graphene oxide (rGO) nanosheets (CMS-rGO NSs). This nanocatalyst was discovered to have an impressive reactivity for in situ generation and synchronistical activation of H2O2 in different active centers, yielding fast and efficient degradation of the pollutants. The reaction rate is ∼21 times higher than that of conventional Fenton catalysts. The characterization shows that countless flower-like CoMoS2 nanospheres are uniformly embedded in the rGO nanosheets through MoSC bonding bridges in CMS-rGO NSs, which leads to activation of the π electrons and their transfer from rGO to the metal centers (π → M). The formed MoOCo further leads to a distribution of orientations of the electrons around the metal centers due to the different electronegativity of Mo and Co. During the reaction, the dissolved O2 is efficiently reduced to HO2/O2- around the electron-rich Mo center, and HO2/O2- is further reduced to H2O2 around the Co center. The generated H2O2 is finally reduced to OH for degrading dyes in the electron-rich metal (Mo or Co) centers of CMS-rGO NSs. The dye pollutants also act as electron donors, and they are directly degraded in the electron-poor π-center of CMS-rGO NSs, which promote the electron transfer cycle and achieve electron gain-loss balance. This discovery provides a new strategy for H2O2 generation-activation and pollutant degradation through constructing electron transfer bridges over the surface of catalysts.

Dianhydrogalactitol, a potential multitarget agent, inhibits glioblastoma migration, invasion, and angiogenesis.

The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in glioblastoma have not been elucidated. Here we show that DAG could inhibit the migration and invasion of U251 cell line by inhibiting matrix metalloproteinase-2 (MMP2) expression. Furthermore, DAG could also inhibit tumor angiogenesis in vitro as well as in the zebrafish model. Mechanistic studies reveal that DAG inhibited both VEGFR2 and FGFR1 pathways. Our results suggest that DAG may be a potential multitarget agent that can inhibit tumor migration, invasion, and angiogenesis, and the anti-angiogenic effects may be involved in dual-suppression VEGF/VEGFR2 and FGF2/FGFR1 signal pathways.

Mechanisms linking employee affective delivery and customer behavioral intentions.

Past empirical evidence has indicated that employee affective delivery can influence customer reactions (e.g., customer satisfaction, service quality evaluation). This study extends previous research by empirically examining mediating processes underlying the relationship between employee affective delivery and customer behavioral intentions. Data were collected from 352 employee-customer pairs in 169 retail shoe stores in Taiwan. Results showed that the influence of employee affective delivery on customers' willingness to return to the store and pass positive comments to friends was indirect through the mediating processes of customer in-store positive moods and perceived friendliness. The study also indicated that employee affective delivery influences customers' time spent in store, which, in turn, influences customer behavioral intentions.