dinoprost and Astrocytoma

Topics: Animals; Antineoplastic Agents; Astrocytes; Astrocytoma; Cell Survival; Cyclooxygenase Inhibitors; Dinoprost; F2-Isoprostanes; Fatty Acids; gamma-Linolenic Acid; Glioma; Ibuprofen; Lipoxygenase Inhibitors; Oxidative Stress; Radiation Tolerance; Rats; Tumor Cells, Cultured

This study compares the effect of gamma-linolenic acid (GLA) and its precursor linoleic acid (LA) on survival of 36B10 malignant rat astrocytoma cells and 'normal' rat astrocytes. GLA was cytotoxic to 36B10 cells but not to astrocytes. By contrast, LA supplementation did not affect the survival of either cell types. There were minor differences in the uptake, distribution and use of radiolabelled GLA and LA by the 36B10 cells and astrocytes. GLA and LA supplementation increased the total polyunsaturated fatty acid (PUFA) content of the cells indicating increased oxidative potential. However, elevated levels of 8-isoprostane, an indicator of increased oxidative stress, were only observed in the GLA supplemented 36B10 cells. Addition of the antioxidant trolox to GLA-enriched 36B10 cells blocked the cytotoxic effect. Further, GLA enhanced the radiation sensitivity of the astrocytoma cells but not the astrocytes; trolox blocked the GLA-mediated increase in astrocytoma cell radiosensitivity. LA did not affect the radiation response of either cell type. While cyclo-oxygenase inhibitors did not affect GLA cytotoxicity, they blocked the enhanced radiation response of GLA-supplemented cells. The lipoxygenase inhibitor NDGA did not affect the toxicity produced by GLA. Thus, GLA is toxic to the neoplastic astrocytoma cells but not to normal astrocytes.

Topics: alpha-Linolenic Acid; Animals; Antineoplastic Agents; Antioxidants; Astrocytes; Astrocytoma; Brain Neoplasms; Cell Death; Chromans; Cyclooxygenase Inhibitors; Dinoprost; F2-Isoprostanes; gamma-Linolenic Acid; Ibuprofen; Indomethacin; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured; Vitamin E

Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD). Previously, we detected the presence of IL-6 in cortices of AD patients. On the other hand, non-steroidal antiinflammatory drugs (NSAIDs), potent inhibitors of prostaglandin synthesis, have been shown to be beneficial in the treatment of AD. Until now, it remained unclear whether and how these two observations were functionally connected. Here, we show that PGs are able to induce IL-6 synthesis in a human astrocytoma cell line. PGE1 and PGE2, but not PGD2 and PGF2 alpha, led to a rapid and transient induction of astrocytic IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1 beta-induced IL-6 mRNA synthesis. These results suggest a possible link between the release of PGs from activated microglia and the astrocytic synthesis of IL-6, which itself may affect neuronal cells, as hypothesized for Alzheimer's disease. Finally we demonstrate that microglia are a strong source of PGE2 synthesis indicating that these cells may act as the origin of the pathogenic cascade.

Topics: Alprostadil; Alzheimer Disease; Arachidonic Acid; Astrocytoma; Dinoprost; Dinoprostone; Humans; Interleukin-1; Interleukin-6; Microglia; Models, Immunological; Models, Neurological; Prostaglandin D2; Prostaglandins; RNA, Messenger; Transcription, Genetic; Tumor Cells, Cultured

Prostaglandins (PGs) and cytokines, such as interleukin-1 (IL-1) and interleukin-6 (IL-6), have been implicated in the etiopathology of various inflammatory and degenerative disorders, including Alzheimer's disease (AD) and prion diseases. Nonsteroidal antiinflammatory drugs (NSAIDs), potent inhibitors of PG synthesis, appear to be beneficial in the treatment of AD. To assess whether PGs are able to induce IL-6 synthesis in cells of the CNS, IL-6 mRNA and protein syntheses were measured in a human astrocytoma cell line after stimulation with different PGs. PGE1 and PGE2, but not PGD2 and PGF2 alpha, led to a rapid and transient induction of IL-6 mRNA, followed by IL-6 protein synthesis. Furthermore, PGE2 potentiated IL-1 beta-induced IL-6 mRNA synthesis. These results are discussed with respect to the participation of PGs in neurodegenerative diseases (and its inhibition by NSAIDs) by affecting cytokine expression.

Topics: Alprostadil; Astrocytoma; Brain; Dinoprost; Dinoprostone; Fluorescent Antibody Technique; Gene Expression Regulation; Humans; Interleukin-1; Interleukin-6; Kinetics; Oxytocics; Prostaglandin D2; RNA, Messenger; Tumor Cells, Cultured; Vasodilator Agents

Tumour cell-rich platelet-free preparations were isolated from 21 fresh samples of human intracranial tumours using enzymic digestion, followed by discontinuous density gradient centrifugation on Percoll and (14 preparations) adherence on plastic. Of the disaggregated cells 79.8 to 97.7% (mean 86.2%) were tumour cells, and mean cell viability was 82.6%. All the tumours produced prostaglandin (PG), E2, F2 alpha, 6 oxo F1 alpha and Thromboxane B2 during 16 hours of incubation but the amount varied widely. Highest production of PGE2 and TXB2 per 10(5) cells was by the eight meningiomas in which the prostanoid profile closely resembled that of circulating monocytes.

Topics: 6-Ketoprostaglandin F1 alpha; Astrocytoma; Brain Neoplasms; Dinoprost; Dinoprostone; Glioblastoma; Glioma; Humans; Meningeal Neoplasms; Meningioma; Monocytes; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane B2; Thromboxanes