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The role of phospholipase (A2PLA2) in tumor cell growth was investigated using SK-N-MC human neuroblastoma cells. 4-Bromophenacyl bromide (BPB) and mepacrine (Mep), known PLA2 inhibitors, suppressed growth of the tumor cells in a dose-dependent manner without a significant cytotoxicity. Melittin (Mel), a PLA2 activator, enhanced the cell growth in a concentration-dependent fashion. The growth-enhancing effects of Mel were significantly reversed by the co-treatment with PLA2 inhibitors. In addition, Mel induced intracellular Ca2+ release from internal stores like as did serum, a known intracellular Ca2+ agonist in the tumor cells. Intracellular Ca2+ release induced by these agonists was significantly blocked by PLA2 inhibitors at growth-inhibitory concentrations. Arachidonic acid (AA), a product of the PLA2?catalyzed reaction, induced cell growth enhancement and intracellular Ca2+ release. These effects of AA were significantly blocked by BAPTA/AM, an intracellular Ca2+ chelator. Taken together, these results suggest that the modulation of PLA2 activity may be one of the regulatory mechanisms of cell growth in human neuroblastoma cells. Intracellular Ca2+ may act as a key mediator in the PLA2?induced growth regulation.
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