Cancer specific inhibitors reflective of unique metabolic needs, are rare. We describe a novel small molecule, Gboxin, that specifically inhibits primary mouse and human glioblastoma (GBM) cell growth but not mouse embryo fibroblasts or neonatal astrocytes. Gboxin rapidly and irreversibly compromises GBM oxygen consumption. Reliant on its positive charge, Gboxin associates with mitochondrial oxidative phosphorylation complexes in a proton gradient dependent manner and inhibits F0F1 ATP synthase activity. Gboxin resistant cells require a functional mitochondrial permeability transition pore that regulates pH impeding matrix accumulation. Administration of a pharmacologically stable Gboxin analog inhibits GBM allografts and patient derived xenografts. Gboxin toxicity extends to established human cancer cell lines of diverse organ origin and exposes the elevated proton gradient pH in cancer cell mitochondria as a new mode of action for antitumor reagent development.
We report measurements of the vacuum ultraviolet (VUV) emission spectra of a microwave-discharge hydrogenflow lamp (MDHL), a common tool in astrochemistry laboratories working on ice VUV photoprocessing. The MDHL provides hydrogen Ly-α (121.6 nm) and H 2 molecular emission in the 110-180 nm range. We show that the spectral characteristics of the VUV light emitted in this range, in particular the relative proportion of Ly-α to molecular emission bands, strongly depend on the pressure of H 2 inside the lamp, the lamp geometry (F type versus T type), the gas used (pure H 2 versus H 2 seeded in He), and the optical properties of the window used (MgF 2 versus CaF 2). These different configurations are used to study the VUV irradiation of CO ice at 14 K. In contrast to the majority of studies dedicated to the VUV irradiation of astrophysical ice analogs, which have not taken into consideration the emission spectrum of the MDHL, our results show that the processes induced by photons in CO ice from a broad energy range are different and more complex than the sum of individual processes induced by monochromatic sources spanning the same energy range, as a result of the existence of multistate electronic transitions and discrepancy in absorption cross sections between parent molecules and products in the Ly-α and H 2 molecular emission ranges.
Context. Methanol is a common component of interstellar and circumstellar ice mantles and is often used as an evolution indicator in star-forming regions. The observations of gas-phase methanol in the interiors of dense molecular clouds at temperatures as low as 10 K suggest that non-thermal ice desorption must be active. Ice photodesorption has been proposed to explain the abundances of gas-phase molecules toward the coldest regions. Aims. Laboratory experiments were performed to investigate the potential photodesorption of methanol toward the coldest regions. Methods. Solid methanol was deposited at 8 K and UV-irradiated at various temperatures starting from 8 K. The irradiation of the ice was monitored by means of infrared spectroscopy and the molecules in the gas phase were detected using quadrupole mass spectroscopy. Fully deuterated methanol was used for confirmation of the results. Results. The photodesorption of methanol to the gas phase was not observed in the mass spectra at different irradiation temperatures. We estimate an upper limit of 3 × 10 −5 molecules per incident photon. On the other hand, photon-induced desorption of the main photoproducts was clearly observed. Conclusions. The negligible photodesorption of methanol could be explained by the ability of UV-photons in the 114−180 nm (10.87−6.88 eV) range to dissociate this molecule efficiently. Therefore, the presence of gas-phase methanol in the absence of thermal desorption remains unexplained. On the other hand, we find CH 4 to desorb from irradiated methanol ice, which was not found to desorb in the pure CH 4 ice irradiation experiments.
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