Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters

Mario Minuzzo, Michele Ceribelli, Marià Pitarque-Martì, Serena Borrelli, Eugenio Erba, Alberto DiSilvio, Maurizio D'Incalci, Roberto Mantovani

Research output: Contribution to journalArticle

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Abstract

Yondelis is a potent DNA-binding anticancer drug isolated from the tunicate Ecteinascidia turbinata currently undergoing phase III clinical trials. We and others have shown selective inhibition to the transcriptional induction of several genes. We tested the hypothesis that Yondelis specifically targets cell-cycle genes. Our analysis on endogenous and transfected reporter systems revealed complex patterns of transcriptional inhibition and, surprisingly, activation. Other inducible systems - the metallothionein and the CYP3A4 promoters - were little affected. We assayed whether interference of DNA binding of the common nuclear factor Y (NF-Y) activator was responsible for the observed inhibition: in vivo chromatin immunoprecipitation analysis in NIH3T3 and HCT116 cells indicates that NF-Y binding is little affected by Yondelis addition. Finally, histone acetylation was modestly affected only on Cdc2 and cyclin B2 but not on other repressed promoters. These data prove that Yondelis is not a general inhibitor of inducible genes, and its selective effects are exerted downstream from transcription factors binding and histone acetyl transferases recruitment.

Original languageEnglish
Pages (from-to)1496-1503
Number of pages8
JournalMolecular Pharmacology
Volume68
Issue number5
DOIs
Publication statusPublished - Nov 2005

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trabectedin
Cell Cycle
Pharmaceutical Preparations
Histones
Cyclin B2
HCT116 Cells
Cytochrome P-450 CYP3A
cdc Genes
Urochordata
Phase III Clinical Trials
Metallothionein
Chromatin Immunoprecipitation
DNA
Acetylation
Transferases
Genes
Transcription Factors

ASJC Scopus subject areas

  • Pharmacology

Cite this

Minuzzo, M., Ceribelli, M., Pitarque-Martì, M., Borrelli, S., Erba, E., DiSilvio, A., ... Mantovani, R. (2005). Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters. Molecular Pharmacology, 68(5), 1496-1503. https://doi.org/10.1124/mol.105.013615

Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters. / Minuzzo, Mario; Ceribelli, Michele; Pitarque-Martì, Marià; Borrelli, Serena; Erba, Eugenio; DiSilvio, Alberto; D'Incalci, Maurizio; Mantovani, Roberto.

In: Molecular Pharmacology, Vol. 68, No. 5, 11.2005, p. 1496-1503.

Research output: Contribution to journalArticle

Minuzzo, M, Ceribelli, M, Pitarque-Martì, M, Borrelli, S, Erba, E, DiSilvio, A, D'Incalci, M & Mantovani, R 2005, 'Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters', Molecular Pharmacology, vol. 68, no. 5, pp. 1496-1503. https://doi.org/10.1124/mol.105.013615
Minuzzo M, Ceribelli M, Pitarque-Martì M, Borrelli S, Erba E, DiSilvio A et al. Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters. Molecular Pharmacology. 2005 Nov;68(5):1496-1503. https://doi.org/10.1124/mol.105.013615
Minuzzo, Mario ; Ceribelli, Michele ; Pitarque-Martì, Marià ; Borrelli, Serena ; Erba, Eugenio ; DiSilvio, Alberto ; D'Incalci, Maurizio ; Mantovani, Roberto. / Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle promoters. In: Molecular Pharmacology. 2005 ; Vol. 68, No. 5. pp. 1496-1503.
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