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New Castanospermine Glycoside Analogues Inhibit Breast Cancer Cell Proliferation and Induce Apoptosis without Affecting Normal Cells

 

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dc.creator Allan, Ghada es
dc.creator Ouadid-Ahidouch, Halima es
dc.creator Sánchez Fernández, Elena Matilde es
dc.creator Risquez Cuadrado, Rocío es
dc.creator García Fernández, José Manuel es
dc.creator Ortiz Mellet, Carmen es
dc.creator Ahidouch, Ahmed es
dc.date.accessioned 2017-04-07T10:19:48Z
dc.date.available 2017-04-07T10:19:48Z
dc.date.issued 2013
dc.identifier.citation Allan, G., Ouadid-Ahidouch, H., Sánchez Fernández, E.M., Risquez Cuadrado, R., García Fernández, J.M., Ortiz Mellet, C. y Ahidouch, A. (2013). New Castanospermine Glycoside Analogues Inhibit Breast Cancer Cell Proliferation and Induce Apoptosis without Affecting Normal Cells. Plos One, 8 (10), e76411-.
dc.identifier.issn 1932-6203 es
dc.identifier.uri http://hdl.handle.net/11441/57348
dc.description.abstract sp2-Iminosugar-type castanospermine analogues have been shown to exhibit anti-tumor activity. However, their effects on cell proliferation and apoptosis and the molecular mechanism at play are not fully understood. Here, we investigated the effect of two representatives, namely the pseudo-S- and C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives SO-OCS and CO-OCS, on MCF-7 and MDA-MB-231 breast cancer and MCF-10A mammary normal cell lines. We found that SO-OCS and CO-OCS inhibited breast cancer cell viability in a concentration- and time-dependent manner. This effect is specific to breast cancer cells as both molecules had no impact on normal MCF-10A cell proliferation. Both drugs induced a cell cycle arrest. CO-OCS arrested cell cycle at G1 and G2/M in MCF-7 and MDA-MB-231cells respectively. In MCF-7 cells, the G1 arrest is associated with a reduction of CDK4 (cyclin-dependent kinase 4), cyclin D1 and cyclin E expression, pRb phosphorylation, and an overexpression of p21Waf1/Cip1. In MDA-MB-231 cells, CO-OCS reduced CDK1 but not cyclin B1 expression. SO-OCS accumulated cells in G2/M in both cell lines and this blockade was accompanied by a decrease of CDK1, but not cyclin B1 expression. Furthermore, both drugs induced apoptosis as demonstrated by the increased percentage of annexin V positive cells and Bax/Bcl-2 ratio. Interestingly, in normal MCF-10A cells the two drugs failed to modify cell proliferation, cell cycle progression, cyclins, or CDKs expression. These results demonstrate that the effect of CO-OCS and SO-OCS is triggered by both cell cycle arrest and apoptosis, suggesting that these castanospermine analogues may constitute potential anti-cancer agents against breast cancer es
dc.description.sponsorship Ministerio de Economía y Competitividad SAF2010-15670 y CTQ2010-15848 es
dc.format application/pdf es
dc.language.iso eng es
dc.publisher Public Library of Science es
dc.relation.ispartof Plos One, 8 (10), e76411-.
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 Internacional *
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ *
dc.subject Antineoplastic Agents es
dc.subject Apoptosis es
dc.subject Breast Neoplasms es
dc.subject Neoplastic es
dc.title New Castanospermine Glycoside Analogues Inhibit Breast Cancer Cell Proliferation and Induce Apoptosis without Affecting Normal Cells es
dc.type info:eu-repo/semantics/article es
dc.type.version info:eu-repo/semantics/publishedVersion es
dc.rights.accessrights info:eu-repo/semantics/openAccess es
dc.contributor.affiliation Universidad de Sevilla. Departamento de Química orgánica es
dc.relation.projectID info:eu-repo/grantAgreement/MINECO/SAF2010-15670 es
dc.relation.projectID info:eu-repo/grantAgreement/MINECO/CTQ2010-15848 es
dc.relation.publisherversion 10.1371/journal.pone.0076411 es
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0076411 es
idus.format.extent 12 p. es
dc.journaltitle Plos One es
dc.publication.volumen 8 es
dc.publication.issue 10 es
dc.publication.initialPage e76411 es
dc.contributor.funder Ministerio de Economía y Competitividad (MINECO). España
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