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dc.contributor.authorDakir, E-Hen_US
dc.contributor.authorPickard, Aen_US
dc.contributor.authorSRIVASTAVA, Ken_US
dc.contributor.authorMcCrudden, CMen_US
dc.contributor.authorGross, SRen_US
dc.contributor.authorLloyd, Sen_US
dc.contributor.authorZhang, S-Den_US
dc.contributor.authorMargariti, Aen_US
dc.contributor.authorMorgan, Ren_US
dc.contributor.authorRudland, PSen_US
dc.contributor.authorEl-Tanani, Men_US
dc.date.accessioned2019-01-09T10:48:54Z
dc.date.available2018-09-04en_US
dc.date.issued2018-10-09en_US
dc.date.submitted2018-11-30T15:11:10.621Z
dc.identifier.issn1949-2553en_US
dc.identifier.urihttps://qmro.qmul.ac.uk/xmlui/handle/123456789/54263
dc.description.abstractPimozide, an antipsychotic drug of the diphenylbutylpiperidine class, has been shown to suppress cell growth of breast cancer cells in vitro. In this study we further explore the inhibitory effects of this molecule in cancer cells. We found that Pimozide inhibited cell proliferation in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells and A549 lung cancer cells. Furthermore, we found that Pimozide also promoted apoptosis as demonstrated by cell cycle arrest and induction of double-strand DNA breaks but did not result in any effect in the non-transformed MCF10A breast cell line. In order to shed new lights into the molecular pathways affected by Pimozide, we show that Pimozide downregulated RAN GTPase and AKT at both protein and mRNA levels and inhibited the AKT signaling pathway in MDA-MB-231 breast cancer cells. Pimozide also inhibited the epithelial mesenchymal transition and cell migration and downregulated the expression of MMPs. Administration of Pimozide showed a potent in vivo antitumor activity in MDA-MB-231 xenograft animal model and reduced the number of lung metastases by blocking vascular endothelial growth factor receptor 2. Furthermore, Pimozide inhibited myofibroblast formation as evaluated by the reduction in α-smooth muscle actin containing cells. Thus, Pimozide might inhibit tumor development by suppressing angiogenesis and by paracrine stimulation provided by host reactive stromal cells. These results demonstrate a novel in vitro and in vivo antitumor activity of Pimozide against breast and lung cancer cells and provide the proof of concept for a putative Pimozide as a novel approach for cancer therapy.en_US
dc.format.extent34889 - 34910en_US
dc.language.isoenen_US
dc.publisherImpact Journalsen_US
dc.relation.ispartofOncotargeten_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.titleThe anti-psychotic drug pimozide is a novel chemotherapeutic for breast canceren_US
dc.typeArticle
dc.rights.holderCopyright: Dakir et al.
dc.identifier.doi10.18632/oncotarget.26175en_US
pubs.issue79en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume9en_US
dcterms.dateAccepted2018-09-04en_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US


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