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dc.contributor.authorGarcía, Víctor
dc.contributor.authorLara Chica, M. Isabel
dc.contributor.authorCantarero, Irene
dc.contributor.authorSterner, Olov
dc.contributor.authorMuñoz, Eduardo
dc.contributor.authorCalzado Canale, Marco Antonio
dc.date.accessioned2017-12-22T10:49:13Z
dc.date.available2017-12-22T10:49:13Z
dc.date.issued2015
dc.identifier.urihttp://hdl.handle.net/10396/15784
dc.description.abstractGaliellalactone (GL) is a fungal metabolite that presents antitumor activities on prostate cancer in vitro and in vivo. In this study we show that GL induced cell cycle arrest in G2/M phase, caspase-dependent apoptosis and also affected the microtubule organization and migration ability in DU145 cells. GL did not induce double strand DNA break but activated the ATR and ATM-mediated DNA damage response (DDR) inducing CHK1, H2AX phosphorylation (fH2AX) and CDC25C downregulation. Inhibition of the ATM/ATR activation with caffeine reverted GL-induced G2/M cell cycle arrest, apoptosis and DNA damage measured by fH2AX. In contrast, UCN-01, a CHK1 inhibitor, prevented GL-induced cell cycle arrest but enhanced apoptosis in DU145 cells. Furthermore, we found that GL did not increase the levels of intracellular ROS, but the antioxidant N-acetylcysteine (NAC) completely prevented the effects of GL on fH2AX, G2/M cell cycle arrest and apoptosis. In contrast to NAC, other antioxidants such as ambroxol and EGCG did not interfere with the activity of GL on cell cycle. GL significantly suppressed DU145 xenograft growth in vivo and induced the expression of fH2AX in the tumors. These findings identify for the first time that GL activates DDR in prostate cancer.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoenges_ES
dc.publisherImpact Journalses_ES
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/es_ES
dc.sourceOncotarget 7:4490-4506 (2015)
dc.subjectGaliellalactonees_ES
dc.subjectCanceres_ES
dc.subjectCell cyclees_ES
dc.subjectATM/ATRes_ES
dc.subjectCHK1es_ES
dc.titleGaliellalactone induces cell cycle arrest and apoptosis through the ATM/ATR pathway in prostate cancer cellses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherversionhttp://dx.doi.org/10.18632/oncotarget.6606es_ES
dc.relation.projectIDJunta de Andalucía. PI-0650-2010es_ES
dc.relation.projectIDJunta de Andalucía. PI-0246-2013es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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