C. Sakakura, E. Sweeney, Tsutomu Shirahama
May 29, 1998
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41
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Journal
Biochemical and biophysical research communications
Abstract
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.