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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 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
Volume14
Issue number5
DOIs
StatePublished - May 1 2013

Fingerprint

irinotecan
Prostatic Neoplasms
Genes
Gene Knockdown Techniques
Synthetic Lethal Mutations
cetrimonium
Tumor Suppressor Genes

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells. / Wissing, Michel D.; Mendonca, Janet; Kim, Eunice; Kim, Eugene; Shim, Joong S.; Kaelber, Nadine S.; Kant, Huub; Hammers, Hans; Commes, Therese; Van Diest, Paul J.; Liu, Jun O.; Kachhap, Sushant K.

In: Cancer Biology and Therapy, Vol. 14, No. 5, 01.05.2013, p. 401-410.

Research output: Contribution to journalArticle

Wissing, MD, Mendonca, J, Kim, E, Kim, E, Shim, JS, Kaelber, NS, Kant, H, Hammers, H, Commes, T, Van Diest, PJ, Liu, JO & Kachhap, SK 2013, 'Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells', Cancer Biology and Therapy, vol. 14, no. 5, pp. 401-410. https://doi.org/10.4161/cbt.23759
Wissing, Michel D. ; Mendonca, Janet ; Kim, Eunice ; Kim, Eugene ; Shim, Joong S. ; Kaelber, Nadine S. ; Kant, Huub ; Hammers, Hans ; Commes, Therese ; Van Diest, Paul J. ; Liu, Jun O. ; Kachhap, Sushant K. / Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells. In: Cancer Biology and Therapy. 2013 ; Vol. 14, No. 5. pp. 401-410.
@article{7a38b5d8a7484d019260767cef92c05c,
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 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.",
keywords = "Cetrimonium bromide (CTAB), Invasion, Irinotecan, N-myc downstream regulated gene 1 (NDRG1), Prostate cancer, Synthetic lethality, Topoisomerase I",
author = "Wissing, {Michel D.} and Janet Mendonca and Eunice Kim and Eugene Kim and Shim, {Joong S.} and Kaelber, {Nadine S.} and Huub Kant and Hans Hammers and Therese Commes and {Van Diest}, {Paul J.} and Liu, {Jun O.} and Kachhap, {Sushant K.}",
year = "2013",
month = "5",
day = "1",
doi = "10.4161/cbt.23759",
language = "English (US)",
volume = "14",
pages = "401--410",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "5",

}

TY - JOUR

T1 - Identification of cetrimonium bromide and irinotecan as compounds with synthetic lethality against NDRG1 deficient prostate cancer cells

AU - Wissing, Michel D.

AU - Mendonca, Janet

AU - Kim, Eunice

AU - Kim, Eugene

AU - Shim, Joong S.

AU - Kaelber, Nadine S.

AU - Kant, Huub

AU - Hammers, Hans

AU - Commes, Therese

AU - Van Diest, Paul J.

AU - Liu, Jun O.

AU - Kachhap, Sushant K.

PY - 2013/5/1

Y1 - 2013/5/1

N2 - 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.

AB - 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.

KW - Cetrimonium bromide (CTAB)

KW - Invasion

KW - Irinotecan

KW - N-myc downstream regulated gene 1 (NDRG1)

KW - Prostate cancer

KW - Synthetic lethality

KW - Topoisomerase I

UR - http://www.scopus.com/inward/record.url?scp=84877858030&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877858030&partnerID=8YFLogxK

U2 - 10.4161/cbt.23759

DO - 10.4161/cbt.23759

M3 - Article

VL - 14

SP - 401

EP - 410

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 5

ER -