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.
Mansilla
Sylvia
S
Instituto de Biologia Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, Josep Samitier 1-5, E-08028 Barcelona, Spain.
Portugal
José
J
D018943:Anthracyclines / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002474:Cell-Free System; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D015394:Molecular Structure; D016329:Sp1 Transcription Factor / Q000737:chemistry* / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
D018943:Anthracyclines; D016329:Sp1 Transcription Factor; C104426:WP 631; D003630:Daunorubicin