title: Growth and biochemical effects of unsymmetrically substituted polyamine analogues in human lung tumor cells 1.
abstract: Three unsymmetrically substituted polyamine analogues demonstrate significant and selective antitumor effects. Each of the analogues N1-ethyl-N11-propargyl-4,8-diazaundecane (PENSpm), N1-ethyl-N11-(cyclobutyl)methyl-4,8-diazaundecane (CBENSpm), and N1-ethyl-N11-(cyclopropyl)methyl-4,8-diazaundecane (CPENSpm) is cytotoxic to a representative non-small-cell lung carcinoma line, NCI H157, while being only growth-inhibitory to a representative small-cell-lung carcinoma line, NCI H82. Cytotoxicity is accompanied by a significant increase in expression of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT) at the levels of activity and steady-state mRNA. These new analogues are significant both for their cell-type-specific activity and as synthetic prototypes for the addition of SSAT-activated functional groups.
authors.affiliation: Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Casero
authors.forename: A R
authors.initials: AR
authors.lastname: Mank
authors.forename: N H
authors.initials: NH
authors.lastname: Saab
authors.forename: R
authors.initials: R
authors.lastname: Wu
authors.forename: W J
authors.initials: WJ
authors.lastname: Dyer
authors.forename: P M
authors.initials: PM
authors.lastname: Woster
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000627:therapeutic use*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D000970:Antineoplastic Agents; D009955:Ornithine Decarboxylase; D011073:Polyamines; D000099228:Diamine N-Acetyltransferase; C093141:N(1)-ethyl-N(11)-(cyclobutyl)methyl-4,8-diazaundecane-1,11-diamine