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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 O Liu, Sushant K Kachhap

Cancer Biol Ther. 2013 May;14(5):401-10.

PMID: 23377825

Abstract:

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 3360 compounds revealed irinotecan and cetrimonium bromide (CTAB) as compounds that exhibited synthetic lethality against NDRG1 deficient PCa cells. A three-dimensional (3-D) 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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP57090-A Cetrimonium bromide Cetrimonium bromide 57-09-0 Price
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