ABSTRACT
Carnosine is an endogenous dipeptide with antiproliferative properties. Here we show that carnosine selectively inhibits proliferation of human glioblastoma cells (U-118-MG) compared to breast (MB231) and oral (Cal27 and FaDu) cancer cells. Carnosine-induced inhibition of U-118-MG proliferation is associated with a significant: decrease in cellular reactive oxygen species levels, increase in manganese superoxide dismutase (MnSOD) and increase in cyclin B1 expression resulting in G2-block. We conclude that the antiproliferative property of carnosine is due to its ability to enhance MnSOD and cyclin B1 expression. These results will be of significance to the potential application of carnosine in brain cancer therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Carnosine/pharmacology , Cyclin B1/genetics , Neuroglia/drug effects , Reactive Oxygen Species/antagonists & inhibitors , Superoxide Dismutase/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin B1/agonists , Cyclin B1/metabolism , Dose-Response Relationship, Drug , G2 Phase Cell Cycle Checkpoints/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Neuroglia/metabolism , Neuroglia/pathology , Organ Specificity , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
The effect of orally administered sublethal doses of 25, 50 and 100 mg/kg of sodium nitrite in drinking water ad lib. for 21 days on the immune response of Balb/c mice was investigated. The immunological parameters were examined at three phases: 1 day (phase A), 1 week (phase B) and 3 weeks (phase C) after the end of exposure to sodium nitrite. A significant decrease in dose-dependent manner was obtained in the following tests: lymphocyte percentages, concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced lymphocyte proliferation assessed by the colorimetric MTT method, natural killer (NK) cell activity against WEHI-164 target cells, as well as IgM and IgG titers against injected sheep erythrocytes. Maximum suppressions were obtained in phase A after treatment with sodium nitrite at 100 mg/kg including lymphocyte count (17.5%), Con A-induced lymphocyte proliferation (40.1%), LPS-induced lymphocyte proliferation (31.4%), IL-2-stimulated NK cell activity (59.2%), unstimulated NK cell activity (59.6%), IgM titer (57.5%) and IgG titer (61.1%). On the other hand, a significant dose-dependent increase in neutrophil count (71.3%) in phase A and phagocytic activation (133%) in the first two phases was obtained using the nitroblue tetrazolium (NBT) assay in the presence of phorbol myristate acetate (PMA). It was found that the immunosuppressive effect of sodium nitrite is reversible after cessation of exposure.
