Tumor Repression of VCaP Xenografts by a Pyrrole-Imidazole Polyamide.

Journal Article (Journal Article)

Pyrrole-imidazole (Py-Im) polyamides are high affinity DNA-binding small molecules that can inhibit protein-DNA interactions. In VCaP cells, a human prostate cancer cell line overexpressing both AR and the TMPRSS2-ERG gene fusion, an androgen response element (ARE)-targeted Py-Im polyamide significantly downregulates AR driven gene expression. Polyamide exposure to VCaP cells reduced proliferation without causing DNA damage. Py-Im polyamide treatment also reduced tumor growth in a VCaP mouse xenograft model. In addition to the effects on AR regulated transcription, RNA-seq analysis revealed inhibition of topoisomerase-DNA binding as a potential mechanism that contributes to the antitumor effects of polyamides in cell culture and in xenografts. These studies support the therapeutic potential of Py-Im polyamides to target multiple aspects of transcriptional regulation in prostate cancers without genotoxic stress.

Full Text

Duke Authors

Cited Authors

  • Hargrove, AE; Martinez, TF; Hare, AA; Kurmis, AA; Phillips, JW; Sud, S; Pienta, KJ; Dervan, PB

Published Date

  • January 2015

Published In

Volume / Issue

  • 10 / 11

Start / End Page

  • e0143161 -

PubMed ID

  • 26571387

Pubmed Central ID

  • PMC4646452

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0143161


  • eng