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J Enzyme Inhib Med Chem ; 30(3): 345-53, 2015 Jun.
Article in English | MEDLINE | ID: mdl-24939101

ABSTRACT

Many cancer cells have high expression of ornithine decarboxylase (ODC) and there is a concerted effort to seek new inhibitors of this enzyme. The aim of the study was to initially characterize the inhibition properties, then to evaluate the cytotoxicity/antiproliferative cell based activity of N-ω-chloroacetyl-l-ornithine (NCAO) on three human cancer cell lines. Results showed NCAO to be a reversible competitive ODC inhibitor (Ki = 59 µM) with cytotoxic and antiproliferative effects, which were concentration- and time-dependent. The EC50,72h of NCAO was 15.8, 17.5 and 10.1 µM for HeLa, MCF-7 and HepG2 cells, respectively. NCAO at 500 µM completely inhibited growth of all cancer cells at 48 h treatment, with almost no effect on normal cells. Putrescine reversed NCAO effects on MCF-7 and HeLa cells, indicating that this antiproliferative activity is due to ODC inhibition.


Subject(s)
Antineoplastic Agents/pharmacology , Ornithine Decarboxylase Inhibitors/pharmacology , Ornithine Decarboxylase/metabolism , Ornithine/analogs & derivatives , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cells, Cultured , Chlorocebus aethiops , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Enzyme Activation/drug effects , HeLa Cells , Hep G2 Cells , Humans , Liver/drug effects , Liver/enzymology , Liver/metabolism , MCF-7 Cells , Male , Molecular Structure , Ornithine/chemical synthesis , Ornithine/chemistry , Ornithine/pharmacology , Ornithine Decarboxylase Inhibitors/chemical synthesis , Ornithine Decarboxylase Inhibitors/chemistry , Rats , Rats, Wistar , Structure-Activity Relationship , Vero Cells
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