ABSTRACT
ABBREVIATIONS: AO: acridine orange; ATM: ATM serine/threonine kinase; CHEK1: checkpoint kinase 1; CHEK2: checkpoint kinase 2; CI: combination index; DMSO: dimethyl sulfoxide; DSBs: double-strand breaks; GBM: glioblastoma; HR: homologous recombination; H2AX: H2A.X variant histone; IHC: immunohistochemistry; LAPTM4B: lysosomal protein transmembrane 4 beta; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; PARP: poly(ADP-ribose) polymerase; RAD51: RAD51 recombinase; SQSTM1: sequestosome 1; SSBs: single-strand breaks; RNF168: ring finger protein 168; XPO1: exportin 1.
Subject(s)
Glioblastoma , Piperazines , Humans , Sequestosome-1 Protein/metabolism , Autophagy , Phthalazines/pharmacology , Proteins/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Membrane Proteins/metabolism , Oncogene Proteins/metabolism , Ubiquitin-Protein Ligases/metabolismABSTRACT
The catalytic/electrocatalytic performance of platinum (Pt) nanostructures highly relates to their morphology. Herein, we propose a facile self-template pyrolysis strategy at high temperature to synthesize one-dimensionally holey Pt nanotubes (Pt-hNTs) using PtII-dimethylglyoxime complex (PtII-DMG) nanorods as the reaction precursor. The coordination capability of DMG results in the generation of PtII-DMG nanorods, whereas the reducibility of DMG at high temperature leads to the reduction of PtII species in PtII-DMG nanorods. During the reaction process, the inside-out Ostwald ripening phenomenon leads to the hollow morphology of Pt-hNTs. Benefiting from the physical characteristics of hollow and holey structure, Pt-hNTs with clean surface show superior electroactivity and durability for catalyzing ethanol electrooxidation as well as hydrogen evolution reaction in alkaline media. Under optimized experimental conditions, the constructed symmetric Pt-hNTs||Pt-hNTs ethanol electrolyzer only requires an electrolysis voltage of 0.40 V to achieve the electrochemical hydrogen production, demonstrating a highly energy saving strategy relative to traditional water electrolysis.
ABSTRACT
BACKGROUND: Resveratrol exerts inhibitory effects on ovarian cancer cells, while its underlying mechanism and critical molecular target(s) have been lesser known. Activations of Wnt, Notch and STAT3 signaling are frequent in ovarian cancers/OCs and supposed to be important for OC formation and progression, while the impacts of resveratrol on these signaling pathways in OC cells remain obscure. METHODS: In this study, two human ovarian cancer cell lines, OVCAR-3 and CAOV-3, were treated by 120 µM resveratrol and their responses to the treatment and the statuses of Wnt, Notch and STAT3 signaling in them were analyzed by multiple experimental approaches. Selective inhibitors of Wnt, Notch or STAT3 signaling were employed to treat OVCAR-3 and CAOV-3 cells to elucidate the significance of individual signaling pathways for ovarian cancers. RESULTS: The results demonstrated distinct inhibitory effects of resveratrol on human ovarian cancer cells in terms of remarkable G1 phase accumulation, increased apoptosis fraction and concurrent suppression of Wnt, Notch and STAT3 signaling as well as their downstream cancer-related gene expression. Treatments with Wnt, Notch or STAT3 selective inhibitor revealed that only AG490, a JAK-specific inhibitor, inhibits OVCAR-3 and CAOV-3 cells in the extent as similar as that of resveratrol. CONCLUSION: Our results suggest the significance of STAT3 activation in the maintenance and survival of ovarian cancer cells. The activated STAT3 signaling is the critical molecular target of resveratrol. Resveratrol would be a promising candidate in the management of ovarian cancers, especially the ones with resistance to conventional therapeutic agents.
