Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells

Michel D. Wissing, Janet Mendonca, Eunice Kim, Eugene Kim, Joong S. Shim, Nadine S. Kaelber, Huub Kant, Hans Hammers, Therese Commes, Paul J. Van Diest, Jun Liu, Sushant Kachhap

Research output: Contribution to journalArticle


The N-myc downstream regulated gene 1 (NDRG1) has been identified as a metastasis-suppressor gene in prostate cancer (PCa). Compounds targeting PCa cells deficient in NDRG1 could potentially decrease invasion/metastasis of PCa. A cell based screening strategy was employed to identify small molecules that selectively target NDRG1 deficient PCa cells. DU-145 PCa cells rendered deficient in NDRG1 expression by a lentiviral shRNA-mediated knockdown strategy were used in the primary screen. Compounds filtered from the primary screen were further validated through proliferation and clonogenic survival assays in parental and NDRG1 knockdown PCa cells. Screening of 3,360 compounds revealed irinotecan and cetrimonium bromide (CTAB) as compounds that exhibited synthetic lethality against NDRG1 deficient PCa cells. A three-dimensional (3D) invasion assay was utilized to test the ability of CTAB to inhibit invasion of DU-145 cells. CTAB was found to remarkably decrease invasion of DU-145 cells in collagen matrix. Our results suggest that CTAB and irinotecan could be further explored for their potential clinical benefit in patients with NDRG1 deficient PCa.

Original languageEnglish (US)
Pages (from-to)401-410
Number of pages10
JournalCancer Biology and Therapy
Issue number5
Publication statusPublished - May 2013



  • Cetrimonium bromide (CTAB)
  • Invasion
  • Irinotecan
  • N-myc downstream regulated gene 1 (NDRG1)
  • Prostate cancer
  • Synthetic lethality
  • Topoisomerase I

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

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