The ribonucleotide reductase inhibitor trimidox induces c-myc and apoptosis of human ovarian carcinoma cells

摘要: Abstract Trimidox (3,4,5-trihydroxybenzohydroxamidoxime), a recently synthesized inhibitor of ribonucleotide reductase (RR), was shown to exert anti-proliferative activities in HL-60 and K562 human leukemia cell lines prolong the life span mice inoculated with L1210 mouse cells. Here we test whether trimidox also exhibits anti-neoplastic properties ovarian carcinoma Since mode action on fate has not been investigated so far, addressed this unresolved item find that polyhydroxybenzoic acid derivative induces apoptosis N.1 cells when tested growth factor deprived medium. Utilizing an improved analysis, based Hoechst 33258 / propidium iodide double staining, is quantified discriminated from necrosis. c-myc expression, which indispensible for cells, expression plasminogen activator urokinase type (upa), supports apoptotic process under more physiological conditions. Surprisingly, does block dNTP synthesis at concentrations and, therefore, independent RR-inhibition. Like TNFα or benzamide riboside, are inducers down-regulates G1 cycle phosphatase cdc25A, whereas cyclin D1 becomes up-regulated. This report shows destroys by inducing them undergo as well corroborating previous investigations demonstrated these depends over-expression survival factors withdrawn.