Sp1 transcription factor as a target for anthracyclines: effects on gene transcription.

The analysis of how anthracyclines interfere with DNA-protein complexes, and the evaluation of their effects on gene transcription, can promote the development of new more specific anti-tumour agents. Daunorubicin and the bisintercalating anthracycline WP631 (which binds more tightly to DNA) have been compared for their ability to inhibit Sp1-DNA interactions and gene transcription. WP631 is more efficient at inhibiting transcription initiation from promoters containing an Sp1-binding site, and it is a potent inhibitor of Sp1-activated transcription both in vitro and in human cell lines. The analysis of gene expression profiles using arrays, which include several genes containing Sp1-putative binding sites, suggests that changes in the transcriptome induce cell cycle arrest and drive a time-dependent response of cells to death stimuli through distinct pathways, which rely on the anthracycline used and its concentration.