benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone has been researched along with taurolidine* in 2 studies
2 other study(ies) available for benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and taurolidine
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Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vascular endothelial growth factor production by taurolidine.
Taurolidine, a derivative of the amino acid taurin, was recently found to display a potent antineoplastic effect both in vitro and in vivo. The authors therefore initiated studies to assess the potential antineoplastic activity of taurolidine in human glioma cell lines and in ex vivo malignant cell cultures. They also studied the mechanisms that induce cell death and the impact of taurolidine on tumor-derived vascular endothelial growth factor (VEGF) production.. Cytotoxicity and clonogenic assays were performed using crystal violet staining. In the cytotoxicity assay 100% of glioma cell lines (eight of eight) and 74% of ex vivo glioma cultures (14 of 19) demonstrated sensitivity to taurolidine, with a mean median effective concentration (EC50) of 51 +/- 28 microg/ml and 56 +/- 23 microg/ml, respectively. Colony formation was inhibited by taurolidine, with a mean EC50 of 7 +/- 3 microg/ml for the cell lines and a mean EC50 of 3.5 +/- 1.7 microg/ml for the ex vivo glioma cultures. On observing this high activity of taurolidine in both assays, the authors decided to evaluate its cell death mechanisms. Fragmentation of DNA, externalization of phosphatidylserine, activation of poly(adenosine diphosphate-ribose) polymerase, loss of the mitochondrial membrane potential followed by a release of apoptosis-inducing factor, and typical apoptotic features were found after taurolidine treatment. Cell death was preceded by the generation of reactive O2 intermediates, which was abrogated by N-acetylcysteine but not by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Moreover, taurolidine also induced suppression of VEGF production on the protein and messenger RNA level, as shown by an enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction.. Given all these findings, taurolidine may be a promising new agent in the treatment of malignant gliomas; it displays a combination of antineoplastic and antiangiogenic activities, inducing tumor cell apoptosis and inhibiting tumor-derived VEGF production. Topics: Acetylcysteine; Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Apoptosis; Brain Neoplasms; Caspase Inhibitors; Cell Line, Tumor; Collagen Type XI; Cysteine Proteinase Inhibitors; Fas Ligand Protein; Gene Expression; Glioma; Humans; Membrane Glycoproteins; Mitochondria; Phosphatidylserines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species; Taurine; Thiadiazines; Vascular Endothelial Growth Factor A | 2005 |
The effects of taurolidine, a novel antineoplastic agent, on human malignant mesothelioma.
Malignant mesothelioma (MM) is a cancer with uniformly poor responses to current therapeutic regimens. This study evaluates whether taurolidine, a novel antineoplastic agent, is effective against human MM cell lines and a murine model of human MM.. Cell growth inhibition and viability assays were performed on REN, LRK, and H28 cell lines after 24-72-h exposure to 0-200 microm taurolidine. Cell cycle analysis with annexin-V binding, terminal deoxynucleotidyl transferase-mediated nick end labeling assay, electron microscopy, and response to the general caspase inhibitor z-VAD-fmk were performed on MM cell lines after 24-72-h exposure to 50-150 microm taurolidine. Athymic mice were given i.p. injections of 20 x 10(6) REN cells, followed by i.p. taurolidine (17.5 or 20 mg), 3 days/week for up to 3 weeks. Tumors were assessed at day 30. All statistical tests were two-sided.. A 72-h exposure of MM cells to taurolidine showed IC50 of 28-42.7 microm and 50% viability at 49.8-135 microm. Annexin V assay for apoptosis revealed significant increases in annexin binding after 24-72-h exposure to 50-150 microm taurolidine (P <0.05), which was significantly inhibited by z-VAD (P <0.05). MM cells exposed to 50-150 microm taurolidine for 24-72 h showed terminal deoxynucleotidyl transferase-mediated nick end labeling staining consistent with apoptosis, as well as structural evidence of apoptosis via electron microscopy. In vivo, there were significant tumor reductions (62 to >99% reduction) for all dosage regimens compared with untreated controls (P <0.001). In addition, all control animals exhibited ascites and diaphragmatic tumors while treated animals did not.. Taurolidine has significant antineoplastic activity against MM in vitro and in vivo, in part, due to tumor cell apoptosis. These findings warrant further study for potential clinical usefulness. Topics: Amino Acid Chloromethyl Ketones; Animals; Annexin A5; Antineoplastic Agents; Apoptosis; Body Weight; Caspases; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Enzyme Inhibitors; Humans; In Situ Nick-End Labeling; Lung Neoplasms; Male; Mesothelioma; Mice; Mice, Nude; Microscopy, Electron; Phosphatidylserines; Taurine; Thiadiazines; Time Factors | 2004 |