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DU145 Prostate Cancer Cells (du145 + prostate_cancer_cell)
Selected AbstractsProstate carcinoma cells selected by long-term exposure to reduced oxygen tension show remarkable biochemical plasticity via modulation of superoxide, HIF-1, levels, and energy metabolismJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2007Jeanne Bourdeau-Heller Cancer cells are able to tolerate levels of O2 that are damaging or lethal to normal cells; we hypothesize that this tolerance is the result of biochemical plasticity which maintains cellular homeostasis of both energy levels and oxidation state. In order to examine this hypothesis, we used different O2 levels as a selective agent during long-term culture of DU145 prostate cancer cells to develop three isogenic cell lines that grow in normoxic (4%), hyperoxic (21%), or hypoxic (1%) O2 conditions. Growth characteristics and O2 consumption differed significantly between these cell lines without changes in ATP levels or altered sensitivity to 2-deoxy- D -glucose, an inhibitor of glycolysis. O2 consumption was significantly higher in the hyperoxic line as was the level of endogenous superoxide. The hypoxic cell line regulated the chemical gradient of the proton motive force (PMF) independent of the electrical component without O2 -dependent changes in Hif-1, levels. In contrast, the normoxic line regulated Hif-1, without tight regulation of the chemical component of the PMF noted in the hypoxic cell line. From these studies, we conclude that selection of prostate cancer cells by long-term exposure to low ambient levels of O2 resulted in cells with unique biochemical properties in which energy metabolism, reactive oxygen species (ROS), and HIF-1, levels are modulated to allow cell survival and growth. Thus, cancer cells exhibit remarkable biochemical plasticity in response to various O2 levels. J. Cell. Physiol. 212:744,752, 2007. © 2007 Wiley-Liss, Inc. [source] Equilibrium loading of cells with macromolecules by ultrasound: Effects of molecular size and acoustic energyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002Héctor R Guzmán Abstract Ultrasound has been shown to deliver small compounds, macromolecules, and DNA into cells, which suggests potential applications in drug and gene delivery. However, the effect of molecular size on intracellular uptake has not been quantified. This study measured the effect of molecule size (calcein, 623 Da; bovine serum albumin, 66 kDa; and two dextrans, 42 and 464 kDa) on molecular uptake and cell viability in DU145 prostate cancer cells exposed to 500 kHz ultrasound. Molecular uptake in viable cells was shown to be very similar for small molecules and macromolecules and found to correlate with acoustic energy exposure. Molecular uptake was seen to be heterogeneous among viable cells exposed to the same ultrasound conditions; this heterogeneity also correlated with acoustic energy exposure. In a fraction of these cells, molecular uptake reached thermodynamic equilibrium with the extracellular solution for the small molecule and all three macromolecules. The results demonstrate that ultrasound provides a means to load viable cells with large numbers of macromolecules, which may be of use for laboratory and possible clinical drug delivery applications. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1693-1701, 2002 [source] Insulin-like growth factor-induced signals activate mitochondrial respirationBIOTECHNOLOGY JOURNAL, Issue 6 2008Hermann Unterluggauer Abstract From experiments with lower eukaryotes it is known that the metabolic rate and also the rate of aging are tightly controlled by the insulin-like growth factor (IGF)/insulin signal transduction pathway. The mitochondrial theory of aging implies that an increased metabolic rate leads to increased mitochondrial activity; increased production of reactive oxygen species due to these alterations would speed up the aging process. To address the question if mitochondrial activity is influenced by insulin/IGF signaling, we have established an experimental system to determine the influence of IGF-I-dependent signaling on mitochondrial function. We used DU145 prostate cancer cells, known for the intact IGF signal transduction pathway, to address the influence of IGF receptor activation on mitochondrial function by high-resolution respirometry. These experiments revealed that indeed mitochondrial function is regulated by IGF signaling, and up-regulation of respiration seems to require phosphoinositide 3-kinase/AKT signaling, but is independent of IGF effects on cell cycle progression. Collectively these data establish a regulatory cross-talk between insulin/IGF signal transduction and mitochondrial function, two major pathways implicated in controlling the rate of aging. [source] Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptorBJU INTERNATIONAL, Issue 3 2003G.O. Hellawell OBJECTIVE To assess the effect of the downregulation of type 1 insulin-like growth factor receptor (IGF1R) on the chemosensitivity of prostate cancer cells. IGF1R is overexpressed by prostate cancer compared with benign prostatic epithelium and IGF1R expression commonly persists in androgen-independent metastatic disease at levels comparable to those in the primary. MATERIALS AND METHODS Human androgen-independent DU145 prostate cancer cells were transfected with IGF1R antisense oligonucleotides or antisense RNA. Transfected cultures were treated with cisplatin, mitoxantrone, paclitaxel or vehicle control, and survival measured using a clonogenic assay. RESULTS Both antisense strategies suppressed IGF1R protein levels to 30,50% of those in control cultures. This was associated with 1.5,2-fold enhancement of sensitivity to cisplatin, mitoxantrone and paclitaxel, and an increase in cisplatin-induced apoptosis. CONCLUSION This approach has potential for development as a clinical treatment for advanced prostate cancer and other chemoresistant tumours. [source] | ||||||||||