The important role of caspase-10 in sodium butyrate-induced apoptosis. 
Butyrate, a short chain fatty acid, exhibits a wide variety of biological effects including the inhibition of cell growth, change of cellular morphology and the induction of apoptosis.  Sodium butyrate-induced apoptosis has been reported to associate with the up-regulation of pro-apoptotic Bax expression, and the down-regulation of anti-apoptotic Bcl-2 and Bcl-XL expressions.  However, in some cases, butyrate has also been shown to cause apoptosis without change in Bcl-2, Bcl-XL and/or Bax.  This study investigates the detailed mechanisms of sodium butyrate-induced apoptosis.  The effect of sodium butyrate was analyzed in the induction of caspase activities, formation of caspase active forms and mRNA levels in human breast cancer cell line MRK-nu-1.  Induction of activities of caspase-3, -10 and, to some extent, -8 and formation of DNA fragmentation were observed with sodium butyrate in a dose- and/or time-dependent manner.  The levels of caspase-10 mRNA expression markedly increased in a time-dependent manner by the treatment of sodium butyrate, whereas caspase-8 mRNA expression was not changed.  Inhibitors of caspase-8 and caspase-10 reduced caspase-3 activity and subsequent DNA fragmentation induced by sodium butyrate.  These caspase inhibitors also inhibited the cleavage of pro-caspase-3 to the active forms indicated by Western blotting analysis.  Pyrrolidine dithiocarbamate also inhibited the induction of caspase-10 mRNA expression and caspase-3 activation.  Contrary to other reports, levels of Bcl-2, Bcl-XL and Bax mRNA expressions were not distinctly changed by even 5 mM sodium butyrate treatment.  Our results suggest that sodium butyrate may trigger apoptosis via the induction of the caspase-10 expression.