Inhibitory effect of mimosine on proliferation of human lung cancer cells is mediated by multiple mechanisms

The plant amino acid mimosine has been reported to block cell cycle progres sion in the late GI phase. A recent study showed that mimosine might induce growth arrest by activating the expression of p21(CIP1), a cyclin-dependen t kinase inhibitor (CDKI), and by inhibiting the activity of cyclin E-assoc iated kinases in human boast cancer cells. However, mimosine at higher conc entrations also blocked proliferation of p21(-/-) cells by unknown mechanis ms. In this study, we investigated the effect of mimosine on the expression of cyclins and CDKIs in human lung cancer cells. We found that mimosine sp ecifically inhibited cyclin D1expression in H226 cells. The expression of a nother G1 cyclin, cyclin E, was not regulated by mimosine in all lung cance r cell lines examined. Moreover, mimosine induced p21(CIP1) expression in H 226 and H358 cells, while it activated p27(KIP1) expression in H322 cells. However, mimosine does not affect transcription of these genes directly bec ause significant changes in cyclin D1 or CDKI expression were observed at 1 2-24 h after drug addition. Our results indicate that mimosine may block ce ll proliferation by multiple mechanisms and this amino acid is a useful age nt for the study of cell cycle control. (C) 1999 Elsevier Science Ireland L td. All rights reserved.