Effects of the proapoptotic drug prodigiosin on cell cycle-related proteins in Jurkat T cells

Abstract

Prodigiosin (PG) is a red pigment produced by Serratia marcescens with immunosuppressive and apoptotic activities. In this study, we sought to examine the effect of PG on cell cycle-related proteins. The antiproliferative activity of PG was tested using human Jurkat leukaemia T cells in culture. PG-inhibited cell proliferation was determined using thymidine incorporation assay. PG-arrested cell cycle was analysed using immunoblot analysis with specific antibodies against cell cycle-related proteins and kinase assays of cdk2. Apoptosis was determined by Hoechst staining and analysis of DNA fragmentation. PG inhibited cyclin E, cdk2, p27 and p21, the induction of the cyclin A-cdk2 and cyclin E-cdk2 kinase activity, and the phosphorylation of Rb in leukaemic Jurkat cells. We confirmed that PG induces apoptosis by the characteristic DNA laddering pattern and condensed nuclei or apoptotic bodies identified by fluorescence microscopy. These results indicate that PG and other family members form a new group of molecules with a common mechanism of action and specific molecular targets, raising the possibility of their therapeutic use as antineoplastic drugs.