To elucidate the mechanism of action of sodium butyrate (NaB), we examined its effect on the expression of some cell cycle-related proteins (cyclins D1 and E, p16(ink4), p21(waf1), p27(kip1)) in 2 human non-small cell lung cancer cell lines (NCI-460 and NCI-H23) characterized by wild- type and mutant TP53, respectively. The growth of both cell lines was inhibited in a dose-dependent manner and this process was accompanied by a modulation of cell cycle-related proteins. In NCI-H460, the p27(kip1) and p16(ink4) protein levels were markedly increased following NaB treatment, whereas p21(waf1) was only slightly elevated, with a peak at 2 mM NaB, and p53 was unaffected by any concentration. By contrast, in NCI-H23, a marked increase in p21(waf1) protein was paralleled by decreased p53 levels, whereas all the other investigated proteins remained stable. The results suggest that NaB blocks the growth of both cell lines by induction of cyclin-dependent kinase inhibitors (in particular, p21(waf1) in NCI-H23 and p27(kip1) and p16(ink4) in NCI-H460) through a p53-dependent or p53-independent mechanism, and open up interesting perspectives for the use of NaB as an alternative or additional strategy in the treatment of non-small cell lung carcinoma.
Copyright 2001 Wiley-Liss, Inc.