Induction of apoptosis in specific cell-lines is an important clinical aspect, that could be triggered by an increase of the intracellular calcium concentration ([Ca2+ ]i). We have shown that arsenic trioxide (As2O3) and cisplatin (CDDP) elevate [Ca2+ ]i by two different mechanisms (As2O3: depletion of intracellular Ca2+ stores; CDDP: influx). The intention of this study was to proove: A) independency of these effects and B) possible synergistic effects triggered by co-applicaton.

As2O3 and/or CDDP were single-/co-applied in human SY-5Y neuroblastoma cells and in mouse hippocampus cells (MHC) (1mM for 60 min. by flow-system at room-temperature). Cells were loaded with Fluo-4 and measurements were taken by confocal laser scanning microscope.

Application of these substances triggers different calcium signals: A) sustained increase and B) transient elevations. Single- appication of As2O3/CDDP induces a sustained-increase of 37±31%/42±15% (SY-5Y) and 74±50%/21±20% (MHC) while co-application of CDDP to As2O3 or As2O3 to CDDP increases [Ca2+ ]i by 70±57%/114±25% (SY-5Y) or 324±198%/137±113% (MHC). Number of fast transient elevations was increased by 40%/30% (As2O3), 74%/36% (CDDP) and 60%/80% (As2O3 + CDDP) (SY-5Y/MHC).

The use of such synergistic effects could possibly increase the efficiency of chemotherapy and reduce side-effects.