Mediation of Intracellular Ca<SUP>2&#8290;</SUP> in the Phospholipase A<SUB>2</SUB>-induced Cell Proliferation in Human Neuroblastoma Cells

Mediation of Intracellular Ca<SUP>2&#8290;</SUP> in the Phospholipase A<SUB>2</SUB>-induced Cell Proliferation in Human Neuroblastoma Cells

<P> The role of phospholipase A<SUB>2</SUB> (PLA<SUB>2</SUB>) in tumor cell growth was investigated using SK-N-MC human neuroblastoma cells. 4-Bromophenacyl bromide (BPB) and mepacrine (Mep), known PLA<SUB>2</SUB> inhibitors, suppressed growth of the tumor cells in a dose-dependent manner without a significant cytotoxicity. Melittin (Mel), a PLA<SUB>2 </SUB>activator, enhanced the cell growth in a concentration-dependent fashion. The growth-enhancing effects of Mel were significantly reversed by the co-treatment with PLA<SUB>2 </SUB>inhibitors. In addition, Mel induced intracellular Ca<SUP>2&#8290;</SUP> release from internal stores like as did serum, a known intracellular Ca<SUP>2&#8290;</SUP> agonist in the tumor cells. Intracellular Ca<SUP>2&#8290;</SUP> release induced by these agonists was significantly blocked by PLA<SUB>2</SUB> inhibitors at growth-inhibitory concentrations. Arachidonic acid (AA), a product of the PLA<SUB>2</SUB>-catalyzed reaction, induced cell growth enhancement and intracellular Ca<SUP>2&#8290;</SUP> release. These effects of AA were significantly blocked by BAPTA/AM, an intracellular Ca<SUP>2&#8290;</SUP> chelator. Taken together, these results suggest that the modulation of PLA<SUB>2</SUB> activity may be one of the regulatory mechanisms of cell growth in human neuroblastoma cells. Intracellular Ca<SUP>2&#8290; </SUP>may act as a key mediator in the PLA<SUB>2</SUB>-induced growth regulation.