Abstract

It was previously demonstrated that [Pt(O,O0-acac)(g-acac)(DMS)] exerted toxic effects at high doses, whilst sub-cytotoxic concentrations induced anoikis and decreased cell migration. Aim of this study was to investigate the hypothesis that [Pt(O,O0-acac)(g-acac)(DMS)] alters the [Ca2+]i and that this is linked to its ability to trigger rapid apoptosis in MCF-7 cells. Thus, cells were treated with [Pt(O,O0-acac)(gacac)( DMS)] and its effects on some of the systems regulating Ca2+ homeostasis were studied, also in cells dealing with the complex changes occurring during the Ca2+ signalling evoked by extracellular stimuli. [Pt(O,O0-acac)(g-acac)(DMS)] caused the decrease of PMCA activity (but not SERCA or SPCA) and Ca2+ membrane permeability. These two opposite effects on [Ca2+]i resulted in its overall increase from 102 12 nM to 250 24 nM after 15 min incubation. The effects of [Pt(O,O0-acac)(g-acac)(DMS)] were also evident when cells were stimulated with ATP: the changes in Ca2+ levels caused by purinergic stimulation resulted altered due to decreased PMCA activity and to the closure of Ca2+ channels opened by purinergic receptor. Conversely, [Pt(O,O0-acac)(g-acac)(DMS)] did not affect the store-operated Ca2+ channels opened by thapsigargin or by ATP. [Pt(O,O0-acac)(g-acac)(DMS)] provoked the activation of PKC-a and the production of ROS that were responsible for the Ca2+ permeability and PMCA activity decrease, respectively. The overall effect of [Pt(O,O0-acac)(g-acac)(DMS)] is to increase the [Ca2+]i, an effect that is likely to be linked to its ability to trigger rapid apoptosis in MCF-7 cells. These data reinforce the notion that [Pt(O,O0-acac)(gacac)( DMS)] would be a promising drug in cancer treatment

Autore Pugliese

• Fanizzi Francesco Paolo , Muscella Antonella , Marsigliante Santo

Tutti gli autori

• A. Muscella , N. Calabriso , C. Vetrugno , F.P. Fanizzi , S.A. De Pascali , C. Storelli , S. Marsigliante .

Titolo volume/Rivista

BIOCHEMICAL PHARMACOLOGY

Anno di pubblicazione

2011

ISSN

0006-2952

ISBN

Non Disponibile

Numero di citazioni Wos

31

Ultimo Aggiornamento Citazioni

28/04/2018

Numero di citazioni Scopus

31

Ultimo Aggiornamento Citazioni

28/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile