title: Binding of Pt-pentamidine to nucleosomal DNA. Studies of the antiproliferative activity of the drug against human cancer cells.
abstract: In the present paper we present data showing that the effect of the binding of the antitumour drug Pt-pentamidine to nucleosomal DNA is the opposite to that of the cis-DDP compound since it causes strong stabilization of the double helix to heat denaturation and because in nucleosome:Pt-pentamidine complexes the nucleosomal denatured DNA is able to reassociate at 71 degrees C. Upon binding, the pentamidine ligand, by itself, also produces stabilization of the nucleosomal DNA but the effect is lower than that induced by Pt-pentamidine. It seems that in Pt-pentamidine:nucleosome complexes about 50% of the adducts are formed during the first hour of incubation of the nucleosomes with the drug since the increase in Tm of the DNA of these complexes is 53% of the total increase in Tm of the DNA of the Pt-pentamidine:nucleosome complexes formed in 48 h. The 'in vitro' screening of the antiproliferative activity of Pt-pentamidine against 60 tumour cell lines indicated that this antitumour compound shows higher antiproliferative activity against small cell lung, non-small cell lung and melanoma cancer lines than against the rest of the cell lines.
authors.affiliation: Centro de Biologia Molecular Severo Ochoa, Facultad de Ciencias, Universidad Autonoma de Madrid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Pérez
authors.forename: J M
authors.initials: JM
authors.lastname: Requena
authors.forename: D
authors.initials: D
authors.lastname: Craciunescu
authors.forename: J C
authors.initials: JC
authors.lastname: Doadrio
authors.forename: C
authors.initials: C
authors.lastname: Alonso
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006358:Hot Temperature; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism; D010419:Pentamidine / Q000378:metabolism* / Q000494:pharmacology; D017671:Platinum Compounds / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D009707:Nucleosomes; D017671:Platinum Compounds; D010419:Pentamidine; D004247:DNA