Indomethacin induces apoptosis via a MRP1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1

Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRP1) function. The doxorubicin-resistant MRP1-overexpressing human SCLC cell line GLC4-Adr was highly sensitive for indomethacin compared with the parental doxorubicin-sensitive line GLC4. The purpose of this study was to analyse the relationship between hypersensitivity to indomethacin and MRP1 overexpression. The experimental design involved analysis of the effect of MRP1 downregulation on indomethacin-induced cell survival and apoptosis in GLC4-Adr and GLC4, using siRNA. In addition the effect of indomethacin on glutathione levels and mitochondrial membrane potential was investigated. Small interfering RNAs directed against MRP1 reduced MRP1 mRNA levels twofold and reduced efflux pump function of MRP1, which was reflected by a 1.8-fold higher accumulation of MRP1 substrate carboxyfluorescein, in si-MRP1 versus si-Luciferase-transfected GLC4-Adr cells. Multidrug resistance protein 1 downregulation decreased initial high apoptosis levels 2-fold in GLC4-Adr after indomethacin treatment for 24 h, and increased cell survival (IC50) from 22.8±2.6 to 30.4±5.1 μM following continuous indomethacin exposure. Multidrug resistance protein 1 downregulation had no effect on apoptosis in GLC4 or on glutathione levels in both lines. Although indomethacin (20 μM) for 2 h decreased glutathione levels by 31.5% in GLC4-Adr, complete depletion of cellular glutathione by L-buthionine (S,R)-sulphoximine only resulted in a small increase in indomethacin-induced apoptosis in GLC4-Adr, demonstrating that a reduced cellular glutathione level is not the primary cause of indomethacin-induced apoptosis. Indomethacin exposure decreased mitochondrial membrane potential in GLC4-Adr cells, suggesting activation of the mitochondrial apoptosis pathway. Indomethacin induces apoptosis in a doxorubicin-resistant SCLC cell line through an MRP1-dependent mechanism. This may have implications for the treatment of patients with MRP1-overexpressing tumours

Synthesis of some methyl 6-O-alkyl-alpha-D-glycopyranosides

Contains fulltext : 28856.pdf (publisher's version ) (Open Access

Tribology and Stability of Organic Monolayers on CrN: A Comparison among Silane, Phosphate, Alkene, and Alkyne Chemistries

The fabrication of chemically and mechanically stable monolayers on the surfaces of various inorganic hard materials is crucial to the development of biomedical/electronic devices. In this Article, monolayers based on the reactivity of silane, phosphonate, 1-alkene, and 1-alkyne moieties were obtained on the hydroxyl-terminated chromium nitride surface. Their chemical stability and tribology were systematically investigated. The chemical stability of the modified CrN surfaces was tested in aqueous media at 60 °C at pH 3, 7, and 11 and monitored by static water contact angle measurements, X-ray photoelectron spectroscopy (XPS), ellipsometry, and Fourier transform infrared reflection absorption spectroscopy (FT-IRRAS). The tribological properties of the resulting organic monolayers with different end groups (fluorinated or nonfluorinated) were studied using atomic force microscopy (AFM). It was found that the fluorinated monolayers exhibit a dramatic reduction of adhesion and friction force as well as excellent wear resistance compared to those of nonfluorinated coatings and bare CrN substrates. The combination of remarkable chemical stability and superior tribological properties makes these fluorinated monolayers promising candidates for the development of robust high-performance devices

Securing Important Strigolactone Key Structures: Orobanchol and 5-Deoxystrigol

Contains fulltext : 158677.pdf (publisher's version ) (Open Access

On the Sulfonylation of Diethyl Galactarate - Some Structural Corrections - Synthesis and Characterization of Derivatives of Diethyl 2,5-Dihydroxyhexa-2,4-Dienoate

Item does not contain fulltex

On the Sulfonylation of Diethyl D,L-Galactarate - Some Structural Corrections

Item does not contain fulltex

Photochemical Covalent Attachment of Alkene-Derived Monolayers onto Hydroxyl-Terminated Silica

The functionalization of optically transparent substrates is of importance, for example, in the field of biosensing. In this article, a new method for modification of silica surfaces is presented that is based on a photochemical reaction of terminal alkenes with the surface. This yields highly hydrophobic surfaces, which are thermally stable up to at least 400 °C. The formed monolayer provides chemical passivation of the underlying surface, according to studies showing successful blocking of platinum atomic layer deposition (ALD). The reaction is photochemically initiated, requiring light with a wavelength below 275 nm. X-ray photoelectron spectroscopy and infrared spectroscopy studies show that the alkenes initially bind to the surface hydroxyl groups in Markovnikov fashion. At prolonged reaction times (>5 h), however, oligomerization occurs, resulting in layer growth normal to the surface. The photochemical nature of the reaction enables the use of photolithography as a tool to constructively pattern silica surfaces. Atomic force microscopy shows that the features of the photomask are well transferred. The newly developed method can complement existing patterning methods on silica that are based on soft lithography