Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay

Abstract Obesity is associated with ~40% of cancer diagnoses but there are currently no effective preventive strategies, illustrating a need for chemoprevention. We previously demonstrated that fibroblast growth factor 2 (FGF2) from adipose tissue stimulates malignant transformation, as measured by...

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Autores principales:	Vanessa Benham, Blair Bullard, Thomas S. Dexheimer, Matthew P. Bernard, Richard R. Neubig, Karen T. Liby, Jamie J. Bernard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ed4f3360f28b4854a3d1704bfd5877cc
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spelling	oai:doaj.org-article:ed4f3360f28b4854a3d1704bfd5877cc2021-12-02T15:08:31ZIdentifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay10.1038/s41598-019-46531-y2045-2322https://doaj.org/article/ed4f3360f28b4854a3d1704bfd5877cc2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46531-yhttps://doaj.org/toc/2045-2322Abstract Obesity is associated with ~40% of cancer diagnoses but there are currently no effective preventive strategies, illustrating a need for chemoprevention. We previously demonstrated that fibroblast growth factor 2 (FGF2) from adipose tissue stimulates malignant transformation, as measured by growth in soft agar, the gold-standard in vitro transformation assay. Because the soft agar assay is unsuitable for high throughput screens (HTS), we developed a novel method using 3D growth in ultra-low attachment conditions as an alternative to growth in agar to discover compounds that inhibit transformation. Treating non-tumorigenic, skin epithelial JB6 P+ cells with FGF2 stimulates growth in ultra-low attachment conditions analogous to growth in the soft agar. This transformation HTS identified picropodophyllin, an insulin growth factor 1 receptor (IGF1R) inhibitor, and fluvastatin, an HMG-CoA reductase inhibitor, as potential chemopreventive agents. These compounds were validated for efficacy using two non-tumorigenic cell lines in soft agar. Another IGF1R inhibitor and other statins were also tested and several were able to inhibit growth in soft agar. This novel 3D HTS platform is fast, robust and has the potential to identify agents for obesity-associated cancer prevention.Vanessa BenhamBlair BullardThomas S. DexheimerMatthew P. BernardRichard R. NeubigKaren T. LibyJamie J. BernardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vanessa Benham Blair Bullard Thomas S. Dexheimer Matthew P. Bernard Richard R. Neubig Karen T. Liby Jamie J. Bernard Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay
description	Abstract Obesity is associated with ~40% of cancer diagnoses but there are currently no effective preventive strategies, illustrating a need for chemoprevention. We previously demonstrated that fibroblast growth factor 2 (FGF2) from adipose tissue stimulates malignant transformation, as measured by growth in soft agar, the gold-standard in vitro transformation assay. Because the soft agar assay is unsuitable for high throughput screens (HTS), we developed a novel method using 3D growth in ultra-low attachment conditions as an alternative to growth in agar to discover compounds that inhibit transformation. Treating non-tumorigenic, skin epithelial JB6 P+ cells with FGF2 stimulates growth in ultra-low attachment conditions analogous to growth in the soft agar. This transformation HTS identified picropodophyllin, an insulin growth factor 1 receptor (IGF1R) inhibitor, and fluvastatin, an HMG-CoA reductase inhibitor, as potential chemopreventive agents. These compounds were validated for efficacy using two non-tumorigenic cell lines in soft agar. Another IGF1R inhibitor and other statins were also tested and several were able to inhibit growth in soft agar. This novel 3D HTS platform is fast, robust and has the potential to identify agents for obesity-associated cancer prevention.
format	article
author	Vanessa Benham Blair Bullard Thomas S. Dexheimer Matthew P. Bernard Richard R. Neubig Karen T. Liby Jamie J. Bernard
author_facet	Vanessa Benham Blair Bullard Thomas S. Dexheimer Matthew P. Bernard Richard R. Neubig Karen T. Liby Jamie J. Bernard
author_sort	Vanessa Benham
title	Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay
title_short	Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay
title_full	Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay
title_fullStr	Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay
title_full_unstemmed	Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay
title_sort	identifying chemopreventive agents for obesity-associated cancers using an efficient, 3d high-throughput transformation assay
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ed4f3360f28b4854a3d1704bfd5877cc
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Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay

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