The association of statins and taxanes: an efficient combination trigger of cancer cell apoptosis.

BACKGROUND: Cancer cell killing might be achieved by the combined use of available drugs. Statins are major anti-hypercholesterolemia drugs, which also trigger apoptosis of many cancer cell types, while docetaxel is a potent microtubule-stabilising agent. METHODS: Here, we looked at the combined effects of lovastatin and docetaxel in cancer cells. RESULTS: Whole transcriptome microarrays in HGT-1 gastric cancer cells demonstrated that lovastatin strongly suppressed expression of genes involved in cell division, while docetaxel had very little transcriptional effects. Both drugs triggered apoptosis, and their combination was more than additive. A marked rise in the cell-cycle inhibitor p21, together with reduction of aurora kinases A and B, cyclins B1 and D1 proteins was induced by lovastatin alone or in combination with docetaxel. The drug treatments induced the proteolytic cleavage of procaspase-3, a drop of the anti-apoptotic Mcl-1 protein, Poly-ADP-Ribose Polymerase and Bax. Strikingly, docetaxel-resistant HGT-1 cell derivatives overexpressing the MDR-1 gene were much more sensitive to lovastatin than docetaxel-sensitive cells. CONCLUSION: These results suggest that the association of lovastatin and docetaxel, or lovastatin alone, shows promise as plausible anticancer strategies, either as a direct therapeutic approach or following acquired P-glycoprotein-dependent resistance.

Label-free analysis of water-polluting parasite by electrochemical impedance spectroscopy.

A new, label-free, real time and non-invasive method is presented to detect the presence of infectious parasites in water and determine accurately their concentration by electrochemical impedance spectroscopy (E.I.S.) using interdigitated microelectrode array. Cryptosporidium parvum was taken as model. Buffer influence on parasite detection was investigated by comparing parasites suspended in purified water versus phosphate buffer saline. It was shown that a low conductive buffer is required for parasite detection. Different suspensions of C. parvum oocysts were measured in purified water. By fitting resulting electrochemical impedance spectrums with an equivalent electrical circuit, solution conductance was extracted. Conductance increased linearly with C. parvum oocyst concentration. The reasons of conductance modification induced by parasite presence are discussed. Cell constant was calculated for circular interdigitated electrode arrays. Thus sample conductivity can be obtained from raw impedance spectrums and it was established that water conductivity was proportional to C. parvum oocyst amount. This relationship can be expressed by: sigma (Sm(-1))=2.88228x10(-6)xC (oocysts/microl)+1.64565x10(-4) with R(2)=0.99. In this way, E.I.S. can be used as a rapid alternative to current parasite counting procedures which consists in fluorescent staining and microscopic observation. The distinction between dead and living parasites by E.I.S. was also approached. Between 10 kHz and 100 kHz, electrochemical impedance showed a difference of 15% between dead and living oocysts.

Epithelial and endothelial expression of the green fluorescent protein reporter gene under the control of bovine prion protein (PrP) gene regulatory sequences in transgenic mice.

The expression of the cellular form of the prion protein (PrP(c)) gene is required for prion replication and neuroinvasion in transmissible spongiform encephalopathies. The identification of the cell types expressing PrP(c) is necessary to understanding how the agent replicates and spreads from peripheral sites to the central nervous system. To determine the nature of the cell types expressing PrP(c), a green fluorescent protein reporter gene was expressed in transgenic mice under the control of 6.9 kb of the bovine PrP gene regulatory sequences. It was shown that the bovine PrP gene is expressed as two populations of mRNA differing by alternative splicing of one 115-bp 5' untranslated exon in 17 different bovine tissues. The analysis of transgenic mice showed reporter gene expression in some cells that have been identified as expressing PrP, such as cerebellar Purkinje cells, lymphocytes, and keratinocytes. In addition, expression of green fluorescent protein was observed in the plexus of the enteric nervous system and in a restricted subset of cells not yet clearly identified as expressing PrP: the epithelial cells of the thymic medullary and the endothelial cells of both the mucosal capillaries of the intestine and the renal capillaries. These data provide valuable information on the distribution of PrP(c) at the cellular level and argue for roles of the epithelial and endothelial cells in the spread of infection from the periphery to the brain. Moreover, the transgenic mice described in this paper provide a model that will allow for the study of the transcriptional activity of the PrP gene promoter in response to scrapie infection.