title: N-ω-chloroacetyl-l-ornithine, a new competitive inhibitor of ornithine decarboxylase, induces selective growth inhibition and cytotoxicity on human cancer cells versus normal cells.
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.
authors.affiliation: Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prol. Carpio y Plan de Ayala , México, D.F. .
authors.forename: Miriam Marlene
authors.initials: MM
authors.lastname: Medina-Enríquez
authors.forename: Verónica
authors.initials: V
authors.lastname: Alcántara-Farfán
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Aguilar-Faisal
authors.forename: José Guadalupe
authors.initials: JG
authors.lastname: Trujillo-Ferrara
authors.forename: Lorena
authors.initials: L
authors.lastname: Rodríguez-Páez
authors.forename: Alba Laura
authors.initials: AL
authors.lastname: Vargas-Ramírez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D015394:Molecular Structure; D009952:Ornithine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D065108:Ornithine Decarboxylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; C000607132:N-omega-chloroacetylornithine; D065108:Ornithine Decarboxylase Inhibitors; D009952:Ornithine; D009955:Ornithine Decarboxylase
keywords: Cancer; HeLa; HepG2; MCF-7; ODC inhibitor; cell proliferation