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

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.