Effects of the proapoptotic drug prodigiosin on cell cycle-related proteins in Jurkat T cells.
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.
Pérez-Tomás
R
R
Departament de Biologia Cel.lular i Anatomia Patològica, Cancer Cell Biology Research Group, Universitat de Barcelona, L'Hospitalet (Barcelona), Spain. rperez@bell.ub.es
Montaner
B
B
D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004396:Coloring Agents; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D005456:Fluorescent Dyes; D006801:Humans; D019169:Jurkat Cells; D011233:Precipitin Tests; D011353:Prodigiosin / Q000302:isolation & purification / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D001562:Benzimidazoles; D018797:Cell Cycle Proteins; D004396:Coloring Agents; D005456:Fluorescent Dyes; D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases; D011353:Prodigiosin; C017807:bisbenzimide ethoxide trihydrochloride; D013936:Thymidine