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Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells
Sheard, Jonathan J. Southam, Andrew D. MacKay, Hannah L. Ellington, Max A. Snow, Martyn D. Farhat, Khanim L. Bunce, Christopher M. Johnson, William E. B.
Sheard, Jonathan J.
Southam, Andrew D.
MacKay, Hannah L.
Ellington, Max A.
Snow, Martyn D.
Farhat, Khanim L.
Bunce, Christopher M.
Johnson, William E. B.
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Abstract
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.
Citation
Sheard JJ et al. (2020). Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells. Biosci Rep (2021) 41 (1): BSR20202505.
Publisher
Portland Press
Journal
Bioscience Reports
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DOI
10.1042/BSR20202505
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Article
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This document is the Accepted Manuscript version of a published work that appeared in final form in Bioscience Reports. To access the final edited and published work see http://dx.doi.org/10.1042/BSR20202505
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ISSN
0144-8463
EISSN
1573-4935