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dc.contributor.authorSheard, Jonathan J.
dc.contributor.authorSoutham, Andrew D.
dc.contributor.authorMacKay, Hannah L.
dc.contributor.authorEllington, Max A.
dc.contributor.authorSnow, Martyn D.
dc.contributor.authorKhanim, Farhat L.
dc.contributor.authorBunce, Christopher M.
dc.contributor.authorJohnson, William E.; orcid: 0000-0002-7247-9087
dc.date.accessioned2021-11-25T02:01:06Z
dc.date.available2021-11-25T02:01:06Z
dc.date.issued2021-01-05
dc.identifierdoi: 10.1042/bsr20202505
dc.identifier.citationBioscience Reports, volume 41, issue 1
dc.identifier.urihttp://hdl.handle.net/10034/626432
dc.descriptionFrom Crossref journal articles via Jisc Publications Router
dc.descriptionHistory: epub 2021-01-05, ppub 2021-01-29
dc.descriptionArticle version: VoR
dc.descriptionPublication status: Published
dc.description.abstractAbstract Drug repurposing is a cost-effective means of targeting new therapies for cancer. We have examined the effects of the repurposed drugs, bezafibrate, medroxyprogesterone acetate and valproic acid on human osteosarcoma cells, i.e., SAOS2 and MG63 compared with their normal cell counterparts, i.e. mesenchymal stem/stromal cells (MSCs). Cell growth, viability and migration were measured by biochemical assay and live cell imaging, whilst levels of lipid-synthesising enzymes were measured by immunoblotting cell extracts. These drug treatments inhibited the growth and survival of SAOS2 and MG63 cells most effectively when used in combination (termed V-BAP). In contrast, V-BAP treated MSCs remained viable with only moderately reduced cell proliferation. V-BAP treatment also inhibited migratory cell phenotypes. MG63 and SAOS2 cells expressed much greater levels of fatty acid synthase and stearoyl CoA desaturase 1 than MSCs, but these elevated enzyme levels significantly decreased in the V-BAP treated osteosarcoma cells prior to cell death. Hence, we have identified a repurposed drug combination that selectively inhibits the growth and survival of human osteosarcoma cells in association with altered lipid metabolism without adversely affecting their non-transformed cell counterparts.
dc.publisherPortland Press Ltd.
dc.rightsLicence for VoR version of this article starting on 2020-12-08: https://creativecommons.org/licenses/by/4.0/
dc.sourcepissn: 0144-8463
dc.sourceeissn: 1573-4935
dc.subjectCell Biology
dc.subjectMolecular Biology
dc.subjectBiochemistry
dc.subjectBiophysics
dc.titleCombined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells
dc.typearticle
dc.date.updated2021-11-25T02:01:05Z


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