title: Might telomerase enzyme be a possible target for trans-Pt(II) complexes?
abstract: Telomerase is a ribonucleoprotein polymerase that synthesizes telomeric DNA (TTAGGG) repeats. Previously, we have studied the effect on telomerase enzyme of several cis-platinum(II) complexes bearing aromatic amines as bulky carrier groups. All these complexes possess cis-geometry, according to the Cleare and Hoschele's rule. Since recent reports have dealt with the anti-cancer activity of trans-platinum compounds, in this study we have investigated the Farrell's prototypical trans-[Pt(Cl)2(pyridine)2], hereafter called trans-PtPy, in order to understand whether it may possess any anti-telomerase activity. The trans-PtPy has low water solubility and requires dimethyl sulfoxide (DMSO) as co-solvent, thus making the biological tests problematic. The effect of trans-PtPy on MCF-7 cell line concerning log-term telomerase inhibition, telomerase-related gene expression, viability, and apoptosis was evaluated. In a cell-free biochemical assay, trans-PtPy showed significant and dose-dependent inhibition of semi-purified telomerase. The bulk of data indicate that trans-PtPy acts as a non-properly selective anti-proliferative agent, although it shows an initial telomerase inhibitory effect. Telomere length reduction seems not to be the main mechanism causing the observed cell apoptosis. For comparison purpose, results on cis-[Pt(Cl)2(pyridine)2], hereafter cis-PtPy, are reported.
authors.affiliation: Dipartimento di Scienze Mediche, Università del Piemonte Orientale A. Avogadro, Via Solaroli 17, I-28100 Novara, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Colangelo
authors.forename: AnnaLisa
authors.initials: A
authors.lastname: Ghiglia
authors.forename: Ilario
authors.initials: I
authors.lastname: Viano
authors.forename: Homa
authors.initials: H
authors.lastname: Mahboobi
authors.forename: AnnaRita
authors.initials: A
authors.lastname: Ghezzi
authors.forename: Claudio
authors.initials: C
authors.lastname: Cassino
authors.forename: Domenico
authors.initials: D
authors.lastname: Osella
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013237:Stereoisomerism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase