Co-application of arsenic trioxide (As2O3) and cisplatin (CDDP) on human SY-5Y neuroblastoma cells has differential effects on the intracellular calcium concentration ([Ca2+]i) and cytotoxicity

Dennis Alexander Günes, Ana Maria Florea, Frank Splettstoesser, Dietrich Busselberg

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Arsenic trioxide (As2O3) and cisplatin (CDDP) are clinically relevant chemotherapeutics which modulate the intracellular calcium concentration ([Ca2+]i) by different mechanisms: As2O3 depletes intracellular calcium stores while CDDP triggers an influx of Ca2+. We investigate whether co-application of As2O3 and CDDP has an effect on [Ca2+]i homeostasis, resulting in an increase of cytotoxicity/apoptosis in human SY-5Y neuroblastoma cells. Confocal imaging with Ca2+-sensitive dye (fluo-4) was used for investigating [Ca2+]i dynamics. The induction of cell death was assayed using Trypan blue exclusion and Hoechst 33347 staining. Application of As2O3 (1 μM) or CDDP (1 μM) increased [Ca2+]i. The largest elevation was observed when the basic [Ca2+]i concentration was low. Both, transient and sustained [Ca2+]i-increases were observed in response to a single application of As2O3 or CDDP. Sustained increase showed clear additive effects when both drugs were co-applied. The magnitude of the [Ca2+]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 As2O3. The sustained [Ca2+]i elevations resulted in increased cytotoxicity and apoptosis. Therefore, co-treatment with CDDP and As2O3 may be a more effective anti-cancer therapy then either agent alone.

Original languageEnglish
Pages (from-to)194-202
Number of pages9
JournalNeuroToxicology
Volume30
Issue number2
DOIs
Publication statusPublished - Mar 2009
Externally publishedYes

Fingerprint

Cytotoxicity
Neuroblastoma
Cisplatin
Calcium
Apoptosis
Trypan Blue
arsenic trioxide
Cell death
Homeostasis
Cell Death
Coloring Agents
Staining and Labeling
Imaging techniques
Pharmaceutical Preparations
Neoplasms

Keywords

  • Arsenic trioxide
  • Calcium signals
  • Cisplatin
  • Co-application
  • Neuroblastoma
  • Synergisms

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology
  • Medicine(all)

Cite this

Co-application of arsenic trioxide (As2O3) and cisplatin (CDDP) on human SY-5Y neuroblastoma cells has differential effects on the intracellular calcium concentration ([Ca2+]i) and cytotoxicity. / Günes, Dennis Alexander; Florea, Ana Maria; Splettstoesser, Frank; Busselberg, Dietrich.

In: NeuroToxicology, Vol. 30, No. 2, 03.2009, p. 194-202.

Research output: Contribution to journalArticle

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