The platinum (II) complex [Pt(O,O′-acac)(γ-acac)(DMS)] alters the intracellular calcium homeostasis in MCF-7 breast cancer cells |
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Authors: | Antonella Muscella Nadia Calabriso Carla Vetrugno Francesco Paolo Fanizzi Sandra Angelica De Pascali Carlo Storelli Santo Marsigliante |
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Institution: | aCell Pathology Lab, Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Universitá di Lecce, Italy;bCell Physiology Lab, Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Universitá di Lecce, Italy;cGeneral and Inorganic Chemistry Lab, Dipartimento di Scienze e Tecnologie Biologiche e Ambientali (Di.S.Te.B.A.), Universitá di Lecce, Italy |
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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 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,O′-acac)(γ-acac)(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,O′-acac)(γ-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,O′-acac)(γ-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,O′-acac)(γ-acac)(DMS)] did not affect the store-operated Ca2+ 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 Ca2+ permeability and PMCA activity decrease, respectively. The overall effect of Pt(O,O′-acac)(γ-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,O′-acac)(γ-acac)(DMS)] would be a promising drug in cancer treatment. |
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Keywords: | Abbreviations: CCE capacitative calcium entry DMEM Dulbecco's modification of Eagle's medium DMS dimethylsulphide ECL enhanced chemiluminescence NBT nitroblue tetrazolium PBS phosphate-buffered saline PKC-α protein kinase C-alpha PMCA plasma membrane calcium ATPase PVDF polyvinylidene difluoride membrane ROS reactive oxygen species SDS sodium dodecyl sulphate |
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