Selectivity of sphingosine-induced apoptosis. Lack of activity of DL-erythyro-dihydrosphingosine

• Published in: Biochemical and biophysical research communications 1998-05, Vol.246 (3), p.827-830
• Main Authors: Sakakura, C, Sweeney, E A, Shirahama, T, Hagiwara, A, Yamaguchi, T, Takahashi, T, Hakomori, S, Igarashi, Y
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Apoptosis; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; DNA Fragmentation; Enzyme Inhibitors - pharmacology; Flow Cytometry; Humans; Mice; Neoplasms, Experimental - metabolism; Protein Kinase C - antagonists & inhibitors; Second Messenger Systems; Sphingosine - analogs & derivatives; Sphingosine - pharmacology; Stereoisomerism; Structure-Activity Relationship; Tumor Cells, Cultured
• ISSN: 0006-291X
• DOI: 10.1006/bbrc.1998.8719

Sphingosine (Sph) is emerging as an intracellular regulator of cellular differentiation and apoptosis (Ohta, et al., Cancer Res., 55, 691-697, 1995). We have recently found that both Sph and its methylated derivative N,N-dimethylsphingosine (DMS) inhibit mitogen-activated protein kinase (MAPK) activity, suggesting that Sph-induced apoptosis may be mediated at least partly through inhibition of MAPK (Sakakura, et al., Int J Oncol, 11, 31-39, 1997). We report in this study that three stereoisomers, D-erythro-Sph, L-threo-Sph, and DL-erythro-dihydrosphingosine, were tested in induction of apoptosis and inhibition of MAPK activity in three different kinds of solid tumor cell lines. D-erythro-Sph was strongest in these effects among three compounds. L-threo-Sphingosine was partly active. On the other hand, DL-erythro-dihydrosphingosine was totally inactive. These results demonstrate the specificity of sphingosine action in induction of apoptosis and inhibition of MAPK, suggesting that Sph may play an important role as a physiological intracellular messenger of apoptosis in these cancer cells.