The platinum (II) complex [Pt(O,O′-acac)(γ-acac)(DMS)] alters the intracellular calcium homeostasis in MCF-7 breast cancer cells

Abstract

It was previously demonstrated that [Pt(O,O′-acac)(γ-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,O′-acac)(γ-acac)(DMS)] alters the [Ca 2+] i and that this is linked to its ability to trigger rapid apoptosis in MCF-7 cells. Thus, cells were treated with [Pt(O,O′-acac)(γ-acac)(DMS)] and its effects on some of the systems regulating Ca 2+ homeostasis were studied, also in cells dealing with the complex changes occurring during the Ca 2+ signalling evoked by extracellular stimuli. [Pt(O,O′-acac)(γ-acac)(DMS)] caused the decrease of PMCA activity (but not SERCA or SPCA) and Ca 2+ membrane permeability. These two opposite effects on [Ca 2+] i resulted in its overall increase from 102 ± 12 nM to 250 ± 24 nM after 15 min incubation. The effects of [Pt(O,O′-acac)(γ-acac)(DMS)] were also evident when cells were stimulated with ATP: the changes in Ca 2+ levels caused by purinergic stimulation resulted altered due to decreased PMCA activity and to the closure of Ca 2+ channels opened by purinergic receptor. Conversely, [Pt(O,O′-acac)(γ-acac)(DMS)] did not affect the store-operated Ca 2+ channels opened by thapsigargin or by ATP. [Pt(O,O′-acac)(γ-acac)(DMS)] provoked the activation of PKC-α and the production of ROS that were responsible for the Ca 2+ permeability and PMCA activity decrease, respectively. The overall effect of [Pt(O,O′-acac)(γ-acac)(DMS)] is to increase the [Ca 2+] 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,O′-acac)(γ-acac)(DMS)] would be a promising drug in cancer treatment.