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Human Glioblastoma Cells (human + glioblastoma_cell)
Selected AbstractsEffects of prolactin on intracellular calcium concentration and cell proliferation in human glioma cellsGLIA, Issue 3 2002Thomas Ducret Abstract Prolactin (PRL) has several physiological effects on peripheral tissues and the brain. This hormone acts via its membrane receptor (PRL-R) to induce cell differentiation or proliferation. Using reverse transcription,polymerase chain reaction (RT-PCR) combined with Southern blot analysis, we detected PRL-R transcripts in a human glioma cell line (U87-MG) and in primary cultured human glioblastoma cells. These transcripts were deleted or not in their extracellular domains. We examined the effects of PRL on intracellular free Ca2+ concentration ([Ca2+]i) in these cells in order to improve our understanding of the PRL transduction mechanism, which is still poorly documented. [Ca2+]i was measured by microspectrofluorimetry using indo-1 as the Ca2+ fluorescent probe. Spatiotemporal aspects of PRL-induced Ca2+ signals were investigated using high-speed fluo-3 confocal imaging. We found that physiological concentrations (0.4,4 nM) of PRL-stimulated Ca2+ entry and intracellular Ca2+ mobilization via a tyrosine kinase,dependent mechanism. The two types of Ca2+ responses observed were distinguishable by their kinetics: one showing a slow (type I) and the other a fast (type II) increase in [Ca2+]i. The amplitude of PRL-induced Ca2+ increases may be sufficient to provoke several physiological responses, such as stimulating proliferation. Furthermore, PRL induced a dose-dependent increase in [3H]thymidine incorporation levels and in cellular growth and survival, detected by the MTT method. These data indicate that PRL induced mitogenesis of human glioma cells. GLIA 38:200,214, 2002. © 2002 Wiley-Liss, Inc. [source] The hemopexin domain of MMP-9 inhibits angiogenesis and retards the growth of intracranial glioblastoma xenograft in nude miceINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Ravesanker Ezhilarasan Abstract Matrix Metalloproteinase-9 (MMP-9) consists of a prodomain, catalytic domain with 3 fibronectin-like type II modules and C-terminal hemopexin-like (PEX) domain. These domains play distinct roles in terms of proteolytic activity, substrate binding and interaction with inhibitors and receptors. To assess the potential of the MMP-9-PEX domain to interfere with tumor progression, we stably transfected human glioblastoma cells with an expression vector containing a cDNA sequence of the MMP-9-PEX. The selected clones exhibited decreased MMP-9 activity and reduced invasive capacity. We assessed how secretion of MMP-9-PEX by glioblastoma cells affects angiogenic capabilities of human microvascular endothelial cells (HMECs) in vitro. MMP-9-PEX conditioned medium treatment caused a reduction in migration of HMECs and inhibited capillary-like structure formation in association with suppression of vascular endothelial growth factor (VEGF) secretion and VEGF receptor-2 protein level. The suppression of HMECs survival by conditioned medium from MMP-9-PEX stable transfectants was associated with apoptosis induction characterized by an increase in cells with a sub-G0/G1 content, fragmentation of DNA, caspase-3, -8 and -9 activation and poly (ADP-ribose) polymerase (PARP) cleavage. A significant tumor growth inhibition was observed in intracranial implants of MMP-9-PEX stable transfectants in nude mice with attenuation of CD31 and MMP-9 protein expression. These results demonstrate that MMP-9-PEX inhibits angiogenic features of endothelial cells and retards intracranial glioblastoma growth. © 2008 Wiley-Liss, Inc. [source] Antitumor activity of a novel antisense oligonucleotide against Akt1JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2009Heejeong Yoon Abstract The AKT pathway is an important therapeutic target for cancer drug discovery as it functions as a main point for transducing extracellular and intracellular oncogenic signals. Moreover, alternations of the AKT pathway have been found in a wide range of cancers. In the present study, we found that an Akt1 antisense oligonucleotide (Akt1 AO) significantly downregulated the expression of AKT1 at both the mRNA and protein levels and inhibited cellular growth at nanomolar concentrations in various types of human cancer cells. Combined treatment of Akt1 AO with several cytotoxic drugs resulted in an additive growth inhibition of Caki-1 cells. The in vivo effectiveness of Akt1 AO was determined using two different xenograft nude mouse models. Akt1 AO (30,mg/kg, i.v. every 48,h) significantly inhibited the tumor growth of nude mouse subcutaneously implanted with U251 human glioblastoma cells after 27 days treatment. Akt1 AO (30,mg/kg, i.p continuously via osmotic pump) also significantly inhibited the tumor formation in nude mice implanted with luciferase-expressing MIA human pancreatic cancer cells (MIA-Luc) after 14 days of treatment. The luciferase signals from MIA-Luc cells were reduced or completely abolished after 2 weeks of treatment and the implanted tumors were barely detectable. Our findings suggest that Akt1 AO alone or in combination with other clinically approved anticancer agents should be further explored and progressed into clinical studies as a potential novel therapeutic agent. J. Cell. Biochem. 108: 832,838, 2009. © 2009 Wiley-Liss, Inc. [source] Biomolecular characterization of human glioblastoma cells in primary cultures: Differentiating and antiangiogenic effects of natural and synthetic PPAR, agonistsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2008E. Benedetti Gliomas are the most commonly diagnosed malignant brain primary tumors. Prognosis of patients with high-grade gliomas is poor and scarcely affected by radiotherapy and chemotherapy. Several studies have reported antiproliferative and/or differentiating activities of some lipophylic molecules on glioblastoma cells. Some of these activities in cell signaling are mediated by a class of transcriptional factors referred to as peroxisome proliferator-activated receptors (PPARs). PPAR, has been identified in transformed neural cells of human origin and it has been demonstrated that PPAR, agonists decrease cell proliferation, stimulate apoptosis and induce morphological changes and expression of markers typical of a more differentiated phenotype in glioblastoma and astrocytoma cell lines. These findings arise from studies mainly performed on long-term cultured transformed cell lines. Such experimental models do not exactly reproduce the in vivo environment since long-term culture often results in the accumulation of further molecular alterations in the cells. To be as close as possible to the in vivo condition, in the present work we investigated the effects of PPAR, natural and synthetic ligands on the biomolecular features of primary cultures of human glioblastoma cells derived from surgical specimens. We provide evidence that PPAR, agonists may interfere with glioblastoma growth and malignancy and might be taken in account as novel antitumoral drugs. J. Cell. Physiol. 217: 93,102, 2008. © 2008 Wiley-Liss, Inc. [source] Cytotoxicity and apoptosis enhancement in brain tumor cells upon coadministration of paclitaxel and ceramide in nanoemulsion formulationsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2008Ankita Desai Abstract The objective of this study was to examine augmentation of therapeutic activity in human glioblastoma cells with combination of paclitaxel (PTX) and the apoptotic signaling molecule, C6 -ceramide (CER), when administered in novel oil-in-water nanoemulsions. The nanoemulsions were formulated with pine-nut oil, which has high concentrations of essential polyunsaturated fatty acid (PUFA). Drug-containing nanoemulsions were characterized for particle size, surface charge, and the particle morphology was examined with transmission electron microscopy (TEM). Epi-fluorescent microscopy was used to analyze nanoemulsion-encapsulated rhodamine-labeled PTX and NBD-labeled CER uptake and distribution in U-118 human glioblastoma cells. Cell viability was assessed with the MTS (formazan) assay, while apoptotic activity of PTX and CER was evaluated with caspase-3/7 activation and flow cytometry. Nanoemulsion formulations with the oil droplet size of approximately 200 nm in diameter were prepared with PTX, CER, and combination of the two agents. When administered to U-118 cells, significant enhancement in cytotoxicity was observed with combination of PTX and CER as compared to administration of individual agents. The increase in cytotoxicity correlated with enhancement in apoptotic activity in cells treated with combination of PTX and CER. The results of these studies show that oil-in-water nanoemulsions can be designed with combination therapy for enhancement of cytotoxic effect in brain tumor cells. In addition, PTX and CER can be used together to augment therapeutic activity, especially in aggressive tumor models such as glioblastoma. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2745,2756, 2008 [source] | ||||||||||