Induction of G2/M arrest and inhibition of c-myc and p53 transcription by WP631 in Jurkat T lymphocytes

Abstract

WP631, a new DNA-binding drug that bisintercalates into DNA with high affinity, seems to be highly cytotoxic against Jurkat T lymphocytes. The purpose of this study was to gain new insights into the mechanisms by which WP631 halts proliferation in this cell type. Treating Jurkat cells with nanomolar concentrations of WP631 roduced G2/M arrest, inhibited the transcription of c-myc and p53 genes, and induced limited apoptosis during the duration of treatment. Suppression of c-myc and p53 expression, and time-dependent decline in c-Myc and p53 protein levels, was associated with growth arrest. A weak interdependence was also found between the potent antiproliferative activity and the apoptotic response; treatment with WP631 for 24-36hr produced arrest in G2/M and allowed for partial DNA repair. Longer treatments with WP631 allowed some repaired cells to re-enter the cell cycle, but produced aneuploidy or apoptosis in others. © 2002 Elsevier Science Inc. All rights reserved.