Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells

Research output: Contribution to journalArticlepeer-review

Authors

  • Jonathan J. Sheard
  • Max A. Ellington
  • Martyn D. Snow
  • William E. Johnson

External organisations

  • Aston University
  • University of Chester
  • The Royal Orthopaedic Hospital NHS Foundation Trust
  • University of Birmingham
  • Chester Medical School

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.

Bibliographic note

Funding Information: This study was funded by the BBSRC [grant number BB/H016570/1 to J.J.S. and W.E.J.] and by Blood Cancer U.K. (to F.L.K. and C.M.B.). Publisher Copyright: © 2021 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

Details

Original languageEnglish
Article numberBSR20202505
Number of pages11
JournalBioscience Reports
Volume41
Issue number1
Early online date8 Dec 2020
Publication statusPublished - 29 Jan 2021

Keywords

  • cell death, cell proliferation, drug repurposing, mesenchymal stem cell, osteosarcoma

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