Sphingosine Suppresses Mesothelioma Cell Proliferation by Inhibiting PKC-δ and Inducing Cell Cycle Arrest at the G0/G1 Phase

Background/Aims: Sphingosine regulates cellular differentiation, cell growth, and apoptosis. The present study aimed at understanding sphingosine-regulated mesothelioma cell proliferation. Methods: Human malignant mesothelioma cells such as NCI-H28, NCI-H2052, NCI-H2452, and MSTO-211H cells were cultured. The siRNA to silence the protein kinase C (PKC)-delta-targeted gene was constructed and transfected into cells. MTT assay, cell cycle analysis using a flow cytometry, and cell-free PKC-delta assay were carried out. Results: For all the cell types sphingosine inhibited cell growth in a concentration (1-100 mu M)-dependent manner. The sphingosine effect was not prevented by rottlerin, an inhibitor of protein kinase C-delta (PKC-delta); conversely, rottlerin further enhanced the sphingosine effect or rottlerin suppressed mesothelioma cell growth without sphingosine. In the cell-free PKC assay, sphingosine attenuated PKC-delta activity. Knocking-down PKC-delta induced cell cycle arrest at the G(0)/G(1) phase and inhibited cell growth. Conclusion: The results of the present study show that sphingosine suppressed mesothelioma cell proliferation by inhibiting PKC-delta, to induce cell cycle arrest at the G(0)/G(1) phase. Copyright (C) 2012 S. Karger AG, Basel