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Sphingosine induces apoptosis in androgen‐independent human prostatic carcinoma DU‐145 cells by suppression of bcl‐X L gene expression
Author(s) -
Shirahama Tsutomu,
Sakakura Chohei,
Sweeney Elizabeth A.,
Ozawa Masayuki,
Takemoto Masakazu,
Nishiyama Kenryu,
Ohi Yoshitada,
Igarashi Yasuyuki
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00304-9
Subject(s) - sphingosine , staurosporine , apoptosis , protein kinase c , sphingosine kinase , ceramide , biology , lipid signaling , microbiology and biotechnology , programmed cell death , cell culture , sphingosine 1 phosphate , cancer research , kinase , biochemistry , receptor , genetics
Our recent studies have suggested that sphingosine, an endogenous protein kinase C (PKC) inhibitor, may mediate apoptosis induced by a phorbol ester (PMA) in human promyelocytic leukemia HL‐60 cells [Ohta et al. Cancer Res. 1995;55:691–697], and that the apoptotic induction by both PMA and sphingosine is accompanied by down‐regulation of bcl‐2, a gene which acts to prevent apoptotic cell death [Sakakura et al. FEBS Lett. 1996;397:177–180]. In this study, we examined the sphingosine‐induced apoptosis of the androgen‐independent human prostatic carcinoma cell line DU‐145, which expresses bcl‐X L and Bax but not bcl‐2, and found that treatment of DU‐145 cells with sphingosine suppressed bcl‐X L in both mRNA and protein levels but did not change bax expression at all. In contrast, in apoptotic cells treated with a PKC inhibitor, staurosporine, no effect on bcl‐X L or bax expression was observed. The initial metabolites of sphingosine in the cells, ceramide and sphingosine 1‐phosphate, failed to induce apoptosis. These results indicate that, in DU‐145 cells, sphingosine, but not its metabolites, induces apoptosis through down‐regulation of bcl‐X L , independently of PKC inhibition. Our present results, together with previous observations, strongly suggest that apoptosis regulatory genes differ according to cell type and apoptosis induction through sphingosine is accompanied by inhibition of either bcl‐2 or bcl‐X L activity in these cells.