title: Sphingosine suppresses mesothelioma cell proliferation by inhibiting PKC-δ and inducing cell cycle arrest at the G(0)/G(1) phase.
abstract: OBJECTIVE
  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)-δ-targeted gene was constructed and transfected into cells. MTT assay, cell cycle analysis using a flow cytometry, and cell-free PKC-δ assay were carried out.
  
  
  RESULTS
  For all the cell types sphingosine inhibited cell growth in a concentration (1-100 µM)-dependent manner. The sphingosine effect was not prevented by rottlerin, an inhibitor of protein kinase C-δ (PKC-δ); conversely, rottlerin further enhanced the sphingosine effect or rottlerin suppressed mesothelioma cell growth without sphingosine. In the cell-free PKC assay, sphingosine attenuated PKC-δ activity. Knocking-down PKC-δ induced cell cycle arrest at the G0/G1 phase and inhibited cell growth.
  
  
  CONCLUSIONS
  The results of the present study show that sphingosine suppressed mesothelioma cell proliferation by inhibiting PKC-δ, to induce cell cycle arrest at the G0/G1 phase.
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Japan. tomoyuki@hyo-med.ac.jp
authors.forename: Hisaya
authors.initials: H
authors.lastname: Okuwa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Akinobu
authors.initials: A
authors.lastname: Gotoh
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tabata
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fukuoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016193:G1 Phase; D006801:Humans; D008654:Mesothelioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016192:Resting Phase, Cell Cycle; D013110:Sphingosine / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D034741:RNA, Small Interfering; C085746:rottlerin; D051745:Protein Kinase C-delta; D013110:Sphingosine