title: Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells.
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.
authors: Department of Clinical Oncology, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Michel D
authors: MD
authors: Wissing
authors: Janet
authors: J
authors: Mendonca
authors: Eunice
authors: E
authors: Kim
authors: Eugene
authors: E
authors: Kim
authors: Joong S
authors: JS
authors: Shim
authors: Nadine S
authors: NS
authors: Kaelber
authors: Huub
authors: H
authors: Kant
authors: Hans
authors: H
authors: Hammers
authors: Therese
authors: T
authors: Commes
authors: Paul J
authors: PJ
authors: Van Diest
authors: Jun O
authors: JO
authors: Liu
authors: Sushant K
authors: SK
authors: Kachhap
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018797:Cell Cycle Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D013501:Surface-Active Agents / Q000494:pharmacology; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D018797:Cell Cycle Proteins; D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D047908:Intracellular Signaling Peptides and Proteins; D000077146:Irinotecan; D034741:RNA, Small Interfering; D013501:Surface-Active Agents; D000099259:N-myc Downstream-Regulated Gene 1 Protein
keywords: N-myc downstream regulated gene 1 (NDRG1); cetrimonium bromide (CTAB); invasion; irinotecan; prostate cancer; synthetic lethality; topoisomerase I
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