{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:55:11Z","timestamp":1776869711084,"version":"3.51.2"},"reference-count":30,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2020,12,8]],"date-time":"2020-12-08T00:00:00Z","timestamp":1607385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>","DOI":"10.1042\/bsr20202505","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T22:00:15Z","timestamp":1607551215000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells"],"prefix":"10.1042","volume":"41","author":[{"given":"Jonathan\u00a0J.","family":"Sheard","sequence":"first","affiliation":[{"name":"Life and Health Sciences, Aston University, Birmingham B4 7ET, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew\u00a0D.","family":"Southam","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah\u00a0L.","family":"MacKay","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Studies, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max\u00a0A.","family":"Ellington","sequence":"additional","affiliation":[{"name":"University Centre Shrewsbury, Guildhall, Frankwell Quay, Shrewsbury SY3 8HQ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martyn\u00a0D.","family":"Snow","sequence":"additional","affiliation":[{"name":"Royal Orthopaedic Hospital, Birmingham B31 2AP, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhat\u00a0L.","family":"Khanim","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher\u00a0M.","family":"Bunce","sequence":"additional","affiliation":[{"name":"School of Biosciences, University of Birmingham, Birmingham B15 2TT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7247-9087","authenticated-orcid":false,"given":"William\u00a0E.","family":"Johnson","sequence":"additional","affiliation":[{"name":"University Centre Shrewsbury, Guildhall, Frankwell Quay, Shrewsbury SY3 8HQ, U.K."},{"name":"Chester Medical School, Faculty of Medicine and Life Sciences, University of Chester, Chester CH1 4BJ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2021,1,5]]},"reference":[{"key":"2021111620351709500_B1","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1002\/cncr.24121","article-title":"Osteosarcoma incidence and survival rates from 1973 to 2004","volume":"115","author":"Mirabello","year":"2009","journal-title":"Cancer"},{"key":"2021111620351709500_B2","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s10555-009-9186-7","article-title":"Osteosarcoma treatment: state of the art","volume":"28","author":"Ta","year":"2009","journal-title":"Cancer Metastasis Rev."},{"key":"2021111620351709500_B3","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/ijc.24320","article-title":"International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons","volume":"125","author":"Mirabello","year":"2009","journal-title":"Int. J. Cancer"},{"key":"2021111620351709500_B4","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/448645a","article-title":"New uses for old drugs","volume":"448","author":"Chong","year":"2007","journal-title":"Nature"},{"key":"2021111620351709500_B5","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1158\/0008-5472.CAN-03-0799","article-title":"Histone deacetylase is a target of valproic acid-mediated cellular differentiation","volume":"64","author":"Gurvich","year":"2004","journal-title":"Cancer Res."},{"key":"2021111620351709500_B6","doi-asserted-by":"publisher","first-page":"4651","DOI":"10.7314\/APJCP.2013.14.8.4651","article-title":"Chloroquine and valproic acid combined treatment in vitro has enhanced cytotoxicity in an osteosarcoma cell line","volume":"14","author":"Wang","year":"2013","journal-title":"Asian Pacific J. Cancer Prevention: APJCP"},{"key":"2021111620351709500_B7","doi-asserted-by":"publisher","first-page":"e8147","DOI":"10.1371\/journal.pone.0008147","article-title":"Combined Bezafibrate and Medroxyprogesterone Acetate: Potential Novel Therapy for Acute Myeloid Leukaemia","volume":"4","author":"Khanim","year":"2009","journal-title":"PLoS ONE"},{"key":"2021111620351709500_B8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1111\/j.1365-2141.2009.08055.x","article-title":"Combined bezafibrate and medroxyprogesterone acetate have efficacy without haematological toxicity in elderly and relapsed acute myeloid leukaemia (AML)","volume":"149","author":"Murray","year":"2010","journal-title":"Br. J. Haematol."},{"key":"2021111620351709500_B9","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1111\/bjh.12681","article-title":"Bezafibrate and medroxyprogesterone acetate in resistant and relapsed endemic Burkitt lymphoma in Malawi; an open-label, single-arm, phase 2 study (ISRCTN34303497)","volume":"164","author":"Molyneux","year":"2014","journal-title":"Br. J. Haematol."},{"key":"2021111620351709500_B10","doi-asserted-by":"publisher","first-page":"2530","DOI":"10.1158\/0008-5472.CAN-15-0202","article-title":"Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated Synthesis of Monounsaturated Fatty Acids","volume":"75","author":"Southam","year":"2015","journal-title":"Cancer Res."},{"key":"2021111620351709500_B11","doi-asserted-by":"publisher","first-page":"716","DOI":"10.18632\/oncotarget.1704","article-title":"Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and cell cycle inhibition","volume":"5","author":"Yen","year":"2014","journal-title":"Oncotarget"},{"key":"2021111620351709500_B12","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.bbrc.2004.12.186","article-title":"Suppression of chondrosarcoma cells by 15-deoxy-\u039412,14-prostaglandin J2 is associated with altered expression of Bax\/Bcl-xL and p21","volume":"328","author":"Shen","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111620351709500_B13","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"2021111620351709500_B14","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14653240600855905","article-title":"Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement","volume":"8","author":"Dominici","year":"2006","journal-title":"Cytotherapy"},{"key":"2021111620351709500_B15","doi-asserted-by":"publisher","first-page":"406","DOI":"10.2144\/04373ST05","article-title":"Inaccuracies in MTS assays: major distorting effects of medium, serum albumin, and fatty acids","volume":"37","author":"Huang","year":"2004","journal-title":"BioTechniques"},{"key":"2021111620351709500_B16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s00280-010-1287-z","article-title":"The histone deacetylase inhibitor valproic acid sensitizes human and canine osteosarcoma to doxorubicin","volume":"67","author":"Wittenburg","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"2021111620351709500_B17","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0167-4889(96)00005-5","article-title":"Potentiation of myeloid differentiation by anti-inflammatory agents, by steroids and by retinoic acid involves a single intracellular target, probably an enzyme of the aldoketoreductase family","volume":"1311","author":"Bunce","year":"1996","journal-title":"Biochimica et Biophysica Acta (BBA) - Mol. Cell Res."},{"key":"2021111620351709500_B18","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1111\/j.1365-2141.1999.01355.x","article-title":"Clofibric acid: a potential therapeutic agent in AML and MDS","volume":"105","author":"Fenton","year":"1999","journal-title":"Br. J. Haematol."},{"key":"2021111620351709500_B19","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/sj.leu.2402843","article-title":"Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease","volume":"17","author":"Fenton","year":"2003","journal-title":"Leukemia"},{"key":"2021111620351709500_B20","doi-asserted-by":"publisher","first-page":"100361","DOI":"10.1016\/j.conctc.2019.100361","article-title":"Single arm phase II trial assessing the safety, compliance with and activity of Bezafibrate and medroxyProgesterone acetate (BaP) therapy against myeloid and lymphoid cancers","volume":"14","author":"Murray","year":"2019","journal-title":"Contemp Clin. Trials Commun."},{"key":"2021111620351709500_B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/14651858.CD011412.pub3","article-title":"Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data","volume":"6","author":"Nevitt","year":"2017","journal-title":"Cochrane Database of Systematic Rev."},{"key":"2021111620351709500_B22","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1042\/bj20021321","article-title":"Histone deacetylases (HDACs): characterization of the classical HDAC family","volume":"370","author":"de Ruijter","year":"2003","journal-title":"Biochem. J."},{"key":"2021111620351709500_B23","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1054\/bjoc.2001.1821","article-title":"Peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition of human hepatocellular carcinoma","volume":"84","author":"Rumi","year":"2001","journal-title":"Br. J. Cancer"},{"key":"2021111620351709500_B24","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1038\/sj.bjc.6600241","article-title":"Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-\u03b3","volume":"86","author":"Nishida","year":"2002","journal-title":"Br. J. Cancer"},{"key":"2021111620351709500_B25","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1080\/09168451.2015.1012149","article-title":"15-Deoxy-Delta(1)(2), (1)(4)-prostaglandin J(2) as an electrophilic mediator","volume":"79","author":"Shibata","year":"2015","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"2021111620351709500_B26","doi-asserted-by":"publisher","first-page":"11459","DOI":"10.1158\/0008-5472.CAN-05-1696","article-title":"Development of Ewing's Sarcoma from Primary Bone Marrow\u2013Derived Mesenchymal Progenitor Cells","volume":"65","author":"Riggi","year":"2005","journal-title":"Cancer Res."},{"key":"2021111620351709500_B27","first-page":"2704","article-title":"Ewing's Sarcoma Family Tumors Are Sensitive to Tumor Necrosis Factor-related Apoptosis-inducing Ligand and Express Death Receptor 4 and Death Receptor 5","volume":"61","author":"Mitsiades","year":"2001","journal-title":"Cancer Res."},{"key":"2021111620351709500_B28","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1158\/1535-7163.MCT-06-0023","article-title":"15-Deoxy-\u039412,14-prostaglandin J2 induces death receptor 5 expression through mRNA stabilization independently of PPAR\u03b3 and potentiates TRAIL-induced apoptosis","volume":"5","author":"Nakata","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"2021111620351709500_B29","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.bbrc.2013.09.024","article-title":"Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration via downregulating the activity of HER2\/PI3K\/AKT signaling pathway in vitro","volume":"440","author":"Wang","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021111620351709500_B30","doi-asserted-by":"publisher","first-page":"e78250","DOI":"10.1371\/journal.pone.0078250","article-title":"Macrophage migration inhibitory factor and stearoyl-CoA desaturase 1: potential prognostic markers for soft tissue sarcomas based on bioinformatics analyses","volume":"8","author":"Takahashi","year":"2013","journal-title":"PLoS ONE"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20202505\/901036\/bsr-2020-2505.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20202505\/901036\/bsr-2020-2505.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T21:00:36Z","timestamp":1637096436000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/41\/1\/BSR20202505\/227181\/Combined-bezafibrate-medroxyprogesterone-acetate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,29]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20202505","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1]]},"published":{"date-parts":[[2021,1]]},"article-number":"BSR20202505"}}