Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

Efficacy of chemotherapy in advanced stages of colorectal tumours is limited. The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells. We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro. CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin. Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substrate-cleavage assays. Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time- and dose-dependently, whereas the hepatoma cells remained unaffected. Apoptosis reached its maximum between 200 and 500 μg ml−1. This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential. Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis. Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated

Solid-Phase Synthesis of Lipidated Ras Peptides Employing the Ellman Sulfonamide Linker

A detailed study on the solid-phase synthesis of lipidated peptides of the Ras family employing the Ellman sulfonamide linker is reported. Using the C-terminal N-Ras sequence, critical issues such as lipidated amino acid resin loading, peptide elongation in the presence of labile groups and optimized conditions for release of the peptides were investigated. A versatile methodology for the synthesis of peptides with diverse lipid motifs and C-terminal methyl esters has accordingly been established

Kiepenheuer Institute Sun Spectrograph (KISS). Phase A2 study Final report

This study shows the feasibility of the KISSpectrograph. The present technical design fulfills the requirements in respect to optical and mechanical performance. The combination of new materials with already space proven techniques has led to a design which is compatible to the Coordinated Instrument Package and fulfills the optical requirements for KISS. Based on the original design the optical performance of KISS has been improved by the use of - field flatteners in the telescope and; - a toroid field lens to improve image quality; - distributed feedback laser diodes for in flight-calibration and alignment; -carbon fibre materials for thermal stability; - high precision spindles and guidances; - flexural pivots with minimum wear out; - a structural housing to minimize distortion of the optics. Requiring of up to 5.10"7 cycles life time (shutter) special attention has to be paid to AIV and product assurance, which are also part of this study. (orig./HM)Available from TIB Hannover: F93B633+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

The palmitoylation machinery is a spatially organizing system for peripheral membrane proteins

Reversible S-palmitoylation of cysteine residues critically controls transient membrane tethering of peripheral membrane proteins. Little is known about how the palmitoylation machinery governs their defined localization and function. We monitored the spatially resolved reaction dynamics and substrate specificity of the core mammalian palmitoylation machinery using semisynthetic substrates. Palmitoylation is detectable only on the Golgi, whereas depalmitoylation occurs everywhere in the cell. The reactions are not stereoselective and lack any primary consensus sequence, demonstrating that substrate specificity is not essential for de-/repalmitoylation. Both palmitate attachment and removal require seconds to accomplish. This reaction topography and rapid kinetics allows the continuous redirection of mislocalized proteins via the post-Golgi sorting apparatus. Unidirectional secretion ensures the maintenance of a proper steady-state protein distribution between the Golgi and the plasma membrane, which are continuous with endosomes. This generic spatially organizing system differs from conventional receptor-mediated targeting mechanisms and efficiently counteracts entropy-driven redistribution of palmitoylated peripheral membrane proteins over all membranes