The platinum (II) complex [Pt(O,O'-acac)(γ-acac)(DMS)] alters the intracellular calcium homeostasis in MCF-7 breast cancer cells.
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±12nM to 250±24nM after 15min 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.
Muscella
Antonella
A
Cell Pathology Lab, Dipartimento di Scienze e Tecnologie Biologiche e Ambientali, Universitá di Lecce, Italy.
Calabriso
Nadia
N
Vetrugno
Carla
C
Fanizzi
Francesco Paolo
FP
De Pascali
Sandra Angelica
SA
Storelli
Carlo
C
Marsigliante
Santo
S
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007811:Lanthanum / Q000008:administration & dosage / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D051571:Protein Kinase C-alpha / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D019831:Sodium-Calcium Exchanger; D007811:Lanthanum; D051571:Protein Kinase C-alpha; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium