Co-application of arsenic trioxide (As(2)O(3)) and cisplatin (CDDP) on human SY-5Y neuroblastoma cells has differential effects on the intracellular calcium concentration ([Ca(2+)](i)) and cytotoxicit
 

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01-03-09 08:51 AM
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Co-application of arsenic trioxide (As(2)O(3)) and cisplatin (CDDP) on human SY-5Y neuroblastoma cells has differential effects on the intracellular calcium concentration ([Ca(2+)](i)) and cytotoxicity.
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Co-application of arsenic trioxide (As(2)O(3)) and cisplatin (CDDP) on human SY-5Y neuroblastoma cells has differential effects on the intracellular calcium concentration ([Ca(2+)](i)) and cytotoxicity.

Neurotoxicology. 2008 Dec 11;

Authors: Günes DA, Florea AM, Splettstoesser F, Büsselberg D

Arsenic trioxide (As(2)O(3)) and cisplatin (CDDP) are clinically relevant chemotherapeutics which modulate the intracellular calcium concentration ([Ca(2+)](i)) by different mechanisms: As(2)O(3) depletes intracellular calcium stores while CDDP triggers an influx of Ca(2+). We investigate whether co-application of As(2)O(3) and CDDP has an effect on [Ca(2+)](i) homeostasis, resulting in an increase of cytotoxicity/apoptosis in human SY-5Y neuroblastoma cells. Confocal imaging with Ca(2+)-sensitive dye (fluo-4) was used for investigating [Ca(2+)](i) dynamics. The induction of cell death was assayed using Trypan blue exclusion and Hoechst 33347 staining. Application of As(2)O(3) (1muM) or CDDP (1muM) increased [Ca(2+)](i). The largest elevation was observed when the basic [Ca(2+)](i) concentration was low. Both, transient and sustained [Ca(2+)](i)-increases were observed in response to a single application of As(2)O(3) or CDDP. Sustained increase showed clear additive effects when both drugs were co-applied. The magnitude of the [Ca(2+)](i)-increase depends on the order of application; the most pronounced effect occurred when the cells were preincubated with CDDP followed by a co-application with As(2)O(3). The sustained [Ca(2+)](i) elevations resulted in increased cytotoxicity and apoptosis. Therefore, co-treatment with CDDP and As(2)O(3) may be a more effective anti-cancer therapy then either agent alone.

PMID: 19118571 [PubMed - as supplied by publisher]