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.
Nohara
Kazunari
K
Department of Molecular Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yokoyama
Yoshiko
Y
Kano
Kazutaka
K
D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology*; D053455:Caspase 10 / Q000096:biosynthesis / Q000502:physiology*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006801:Humans; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D013859:Thiocarbamates / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D002087:Butyrates; D061945:Caspase Inhibitors; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D053455:Caspase 10