Non-Small Cell Lung Carcinoma Cell Motility, Rac Activation and Metastatic Dissemination Are Mediated by Protein Kinase C Epsilon

Background: Protein kinase C (PKC) e, a key signaling transducer implicated in mitogenesis, survival, and cancer progression, is overexpressed in human primary non-small cell lung cancer (NSCLC). The role of PKCe in lung cancer metastasis has not yet been established. Principal Findings: Here we show that RNAi-mediated knockdown of PKCe in H358, H1299, H322, and A549 NSCLC impairs activation of the small GTPase Rac1 in response to phorbol 12-myristate 13-acetate (PMA), serum, or epidermal growth factor (EGF). PKCe depletion markedly impaired the ability of NSCLC cells to form membrane ruffles and migrate. Similar results were observed by pharmacological inhibition of PKCe with eV1-2, a specific PKCe inhibitor. PKCe was also required for invasiveness of NSCLC cells and modulated the secretion of extracellular matrix proteases and protease inhibitors. Finally, we found that PKCe-depleted NSCLC cells fail to disseminate to lungs in a mouse model of metastasis. Conclusions: Our results implicate PKCe as a key mediator of Rac signaling and motility of lung cancer cells, highlighting its potential as a therapeutic target

1-(12-Azido-n-dodecyl)-4-[(1,5-dibenzyl-2,4-dioxo-2,3,4,5-tetrahydro-1 H-1,5-benzodiazepin-3-yl)methyl]-1H-1,2,3-triazole

The reaction of 1,5-dibenzyl-3-propargyl-1,5-benzodiazepine-2,4-dione with 1,12-diazido-n-dodecane in the presence of catalysts leads to the formation of the title compound, C(38)H(46)N(8)O(2). The seven-membered diazepinyl ring adopts a boat conformation with the azidododecyltriazolylmethyl-bearing C atom as the prow and the fused-ring C atoms as the stern. The octyltriazolylmethyl substituent occupies an axial position

Hydrodynamique dans les milieux gaz/liquide non-newtoniens, agités mécaniquement, étude de l'hélice à profil mince [HPM] et de la turbine à disque de Rushton

The power consumption is measured for non-newtonian gas-liquid systems. The useful zone situated beyond the flooding point was defined by using the power caracteristics plot and hydrodynamic observations. Correlations were established in dimensional or adimensional form, to estimate the stirrer speed at the flooding point, and the power consumption in the working zone. Those correlations established in a large scale of rheological behaviour, for two kind of impellers in different geometrical ratios and for two tanks for scaling up, are used to compare an axial impeller (the thinny profile propeller) to a radial one (the Rushton's disc turbine)

In Vitro Evaluation of the Multidrug Resistance Reversing Activity of Novel Imidazo[4,5-b]pyridine Derivatives

BACKGROUND/AIM: Malignant diseases present a significant public health burden worldwide and their treatment is further complicated by the phenomenon of multidrug resistance. Derivatives of imidazopyridine exhibit several remarkable pharmacological activities and they could reverse the multidrug resistance of cancer cells due to overexpressing P-glycoprotein. MATERIALS AND METHODS: A series of novel imidazo[4,5-b]pyridine derivatives were synthesized and their biological activities were evaluated in vitro using parental (PAR) and multidrug resistant (MDR; ABCB1-overexpressing) mouse T-lymphoma cells. The cytotoxic activity and selectivity of the tested compounds were assessed by the thiazolyl blue tetrazolium bromide (MTT) assay, the ABCB1 modulating activity was measured by rhodamine 123 accumulation assay using flow cytometry. RESULTS: Six compounds (b, c, d, f, h and i) showed moderate-to-high cytotoxic activity on the tested cell lines, while derivative i presented with promising selectivity towards the MDR cell line. Derivatives a, d, f, g and i were proven to be effective modulators of the ABCB1 multidrug efflux pump, with two compounds showing efflux pump modulatory activity at 2 muM concentration. CONCLUSION: Based on our experimental results, compounds that showed potent activity are those with a short carbon side chain; a methoxy group on the benzene ring; a heterocyclic (triazole) side chain and the presence of an alkylated N-atom at position 4