Korean J Physiol Pharmacol.
1998 Aug;2(4):411-417.
Mediation of intracellular Ca2+ in the phospholipase A2-induced cell
proliferation in human neuroblastoma cells
- Affiliations
-
- 1Department of Physiology, College of Pharmacy, Yeungnam University, Kyongsan 712-749, Korea.
- 2Department of Physiology, College of Medicine, Kwandong University, Kangnung 210-701, Korea.
Abstract
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The role of phospholipase A2 (PLA2) 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.