Prolonged ERK Activation of S1P on B16 Melanoma Cells.
- Author:
Hyun Sook LEE
1
;
Gwang Seong CHOI
;
Jeong Hyun SHIN
Author Information
1. Department of Dermatology, Inha University School of Medicine, Incheon, Korea. jshin@inha.ac.kr
- Publication Type:Original Article
- Keywords:
Apoptosis;
Caspase;
ERK;
Melanoma;
Sphingosine 1-phosphate
- MeSH:
Apoptosis;
Blotting, Western;
Caspase 3;
Caspase 8;
Caspases;
Cell Membrane;
Cytochromes c;
Humans;
Lysophospholipids;
Melanoma;
Melanoma, Experimental;
Neurons;
Proteins;
Sphingosine
- From:Korean Journal of Dermatology
2008;46(6):769-775
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: The bioactive sphingolipid metabolite sphingosine 1-phosphate (S1P), was reported to induce apoptosis of some cancer cells and neurons, although it is generally known to exert mitogenic and antiapoptotic effects. Recently, it was described that S1P induced time- and dose-dependent apoptosis in B16 melanoma cells, that was not associated with cell membrane receptors for S1P but ERK and caspase-3 activation. OBJECTIVE: In this study, we aimed to investigate the exact mechanism of apoptosis by S1P using cultured B16 melanoma cells with caspase activity assay and Western blot assays for p-ERK, Fas, Bcl-2 family and cytochrome C proteins. METHODS: We cultured B16 melanoma cells and treated S1P with various concentrations and time. Caspases (3, 8, and 9) activity assay and Western blot assays for phosphor-ERK, Fas, Bcl-2 family and cytochrome C proteins were performed. RESULTS: We observed S1P induced caspase-3, -8, and -9 activations in our results. S1P also induced prolonged activation of ERK in 72 hours. S1P concomitantly increased Bcl-2 protein expression in the early 12 hours of the treatment. Neither fas nor cytochrome C were affected by S1P. CONCLUSION: In conclusion, we propose that S1P may induce apoptotic signal on B16 melanoma cells by prolonged ERK activation and caspase-8, -9, -3 activations. S1P also appears to exert antiapoptotic signal by increasing Bcl-2 protein.
