title: Potentiation of cisplatin-induced antiproliferative and apoptotic activities by the antiarrhythmic drug procainamide hydrochloride.
abstract: BACKGROUND
  We describe the potentiation of antiproliferative and apoptotic activities triggered by cis-diamminedichloroplatinum(II) (DDP), and obtained in vitro by the co-administration of procainamide hydrochloride (PdHCl) in murine P388, and human A2780 and A549 cells.
  
  
  METHODS
  We determined the antiproliferative and apoptotic activities of DDP and PdHCl combinations by different techniques. Moreover, cell cycle analysis, restriction enzyme inhibition followed by agarose gel electrophoresis, and TUNEL analysis of tumour cells in vivo were also used to strengthen our hypothesis.
  
  
  RESULTS
  Our results show that PdHCl may significantly increase the inhibition of cell proliferation and apoptosis. Experiments in vivo showed that the co-administration of DDP and PdHCl increased the percentage of apoptotic cells compared to DDP alone treatment, both in subcutaneous (sc) and intraperitoneal (ip) P388 tumours. We finally demonstrated that the co-administration of PdHCl prevents DNA digestion accounting for a restriction enzyme inhibition that in some cases was greater than that obtained by DDP alone. Moreover, when PdHCl was mixed with the reaction products (RP) of DDP (RP-PdHCl) we obtained a restriction enzyme inhibition greater for some enzymes (Bsp1407I, Hin1II, and Psp1406I) than that obtained by the DDP-PdHCl solution.
  
  
  CONCLUSIONS
  On the whole our data demonstrate that the class I antiarrhythmic drug PdHCl may increase the antiproliferative activity of DDP by improving its triggering of apoptosis, and that this phenomenon may be likely linked to the formation of a new Pt compound.
authors.affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, U.O.C. Bioterapie, Genova, Italy. Electronic address: maurizio.viale@hsanmartino.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
authors.affiliation: Dipartimento di Biologia e Biotecnologie, Università di Pavia, Pavia, Italy. Electronic address: fenoglio@unipv.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Fenoglio
authors.affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, U.O.C. Trasferimento Genico, Genova, Italy. Electronic address: daniela.detotero@hsanmartino.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: de Totero
authors.affiliation: Istituto Giannina Gaslini, U.O.C Laboratorio di Oncologia, Genova, Italy. Electronic address: ignaziaprigione@ospedale-gaslini.ge.it.
authors.forename: Ignazia
authors.initials: I
authors.lastname: Prigione
authors.affiliation: Dipartimento di Scienze Biomediche e Oncologia Umana, Università degli Studi di Bari, Ospedale Consorziale Policlinico, Bari, Italy. Electronic address: lianacassano@libero.it.
authors.forename: Amalia
authors.initials: A
authors.lastname: Cassano
authors.affiliation: Dipartimento di Scienze Biomediche e Oncologia Umana, Università degli Studi di Bari, Ospedale Consorziale Policlinico, Bari, Italy. Electronic address: a.vincenti@libero.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Vincenti
authors.affiliation: Istituto Giannina Gaslini, U.O.C Laboratorio di Oncologia, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bocca
authors.affiliation: IRCCS Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, U.O.C. Bioterapie, Genova, Italy. Electronic address: rosaria.gangemi@hsanmartino.it.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gangemi
authors.affiliation: Dipartimento di Scienze Biomediche e Oncologia Umana, Università degli Studi di Bari, Ospedale Consorziale Policlinico, Bari, Italy. Electronic address: mariaaddolorata.mariggio@uniba.it.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mariggiò
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D051379:Mice; D011342:Procainamide / Q000494:pharmacology*; D015183:Restriction Mapping
chemical_list: D000889:Anti-Arrhythmia Agents; D011342:Procainamide; D002945:Cisplatin
keywords: Antiproliferative activity; Apoptosis; Cis-diamminedichloroplatinum(II); Procainamide hydrochloride; Restriction enzymes