Potentiation of cisplatin-induced antiproliferative and apoptotic activities by the antiarrhythmic drug procainamide hydrochloride

Maurizio Viale, Carla Fenoglio, Daniela De Totero, Ignazia Prigione, Amalia Cassano, Alessandra Vincenti, Paola Bocca, Rosaria Gangemi, Maria A. Mariggiò

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)654-661
Number of pages8
JournalPharmacological Reports
Volume68
Issue number3
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Procainamide
Anti-Arrhythmia Agents
Cisplatin
Enzymes
Apoptosis
Restriction Mapping
Agar Gel Electrophoresis
In Situ Nick-End Labeling
Digestion
Neoplasms
Cell Cycle
Cell Proliferation

Keywords

  • Antiproliferative activity
  • Apoptosis
  • Cis-diamminedichloroplatinum(II)
  • Procainamide hydrochloride
  • Restriction enzymes

ASJC Scopus subject areas

  • Pharmacology

Cite this

Potentiation of cisplatin-induced antiproliferative and apoptotic activities by the antiarrhythmic drug procainamide hydrochloride. / Viale, Maurizio; Fenoglio, Carla; De Totero, Daniela; Prigione, Ignazia; Cassano, Amalia; Vincenti, Alessandra; Bocca, Paola; Gangemi, Rosaria; Mariggiò, Maria A.

In: Pharmacological Reports, Vol. 68, No. 3, 01.06.2016, p. 654-661.

Research output: Contribution to journalArticle

Viale, Maurizio ; Fenoglio, Carla ; De Totero, Daniela ; Prigione, Ignazia ; Cassano, Amalia ; Vincenti, Alessandra ; Bocca, Paola ; Gangemi, Rosaria ; Mariggiò, Maria A. / Potentiation of cisplatin-induced antiproliferative and apoptotic activities by the antiarrhythmic drug procainamide hydrochloride. In: Pharmacological Reports. 2016 ; Vol. 68, No. 3. pp. 654-661.
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T1 - Potentiation of cisplatin-induced antiproliferative and apoptotic activities by the antiarrhythmic drug procainamide hydrochloride

AU - Viale, Maurizio

AU - Fenoglio, Carla

AU - De Totero, Daniela

AU - Prigione, Ignazia

AU - Cassano, Amalia

AU - Vincenti, Alessandra

AU - Bocca, Paola

AU - Gangemi, Rosaria

AU - Mariggiò, Maria A.

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

KW - Antiproliferative activity

KW - Apoptosis

KW - Cis-diamminedichloroplatinum(II)

KW - Procainamide hydrochloride

KW - Restriction enzymes

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