J Korean Med Sci.  2007 Apr;22(2):298-304. 10.3346/jkms.2007.22.2.298.

Sphingosine 1-Phosphate Triggers Apoptotic Signal for B16 Melanoma Cells via ERK and Caspase Activation

Affiliations
  • 1Department of Dermatology, School of Medicine, Inha University, Incheon, Korea.
  • 2Department of Dermatology, School of Medicine, Ajou University, Suwon, Korea.
  • 3Department of Dermatology, Ewha Womans University Mokdong Hospital, 911-1 Mock-dong, Yangcheon-gu, Seoul, Korea. kbmyung@ewha.ac.kr

Abstract

The bioactive sphingolipid metabolite sphingosine 1-phosphate (S1P), recently was reported to induce apoptosis of some cancer cells and neurons, although it generally known to exert mitogenic and antiapoptotic effects. In this study, we investigated the effects of S1P on the cell growth, melanogenesis, and apoptosis of cultured B16 mouse melanoma cells. In results, S1P was found to induce apoptosis in B16 melanoma cells in a dose- and time-dependent manner, but exerted minimal effects on melanogenesis. Although receptors of sphingosine 1-phosphate (endothelial differentiation gene 1 [Edg]/S1P1, Edg5/S1P2, Edg3/S1P3) were expressed in B16 melanoma cells, they were shown not to be associated with S1P-induced apoptosis. In addition, pertussis toxin did not block the apoptotic effects of S1P on B16 melanoma cells. S1P induced caspase-3 activation and the extracellular signal-regulated kinase (ERK) activation. Interestingly, the ERK pathway inhibitor, UO126, reversed the apoptotic effects of S1P on B16 melanoma cells. These results suggest that S1P induced apoptosis of B16 melanoma cells via an Edg receptor-independent, pertussis toxin-insensitive pathway, and appears to be associated with the ERK and caspase-3 activation.

Keyword

Sphingosine 1-Phosphate; Melanoma; Apoptosis; Caspases; Extracellular Signal-Regulated Kinase

MeSH Terms

Sphingosine/administration & dosage/*analogs & derivatives
Signal Transduction/drug effects
Mice
Melanoma/*enzymology/*pathology
Lysophospholipids/*administration & dosage
Extracellular Signal-Regulated MAP Kinases/*metabolism
Enzyme Activation/drug effects
Cell Line
Caspase 3/*metabolism
Apoptosis/*drug effects
Animals
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