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dc.contributor.authorRoel, María
dc.contributor.authorRubiolo, Juan A.
dc.contributor.authorGuerra-Varela, Jorge
dc.contributor.authorSilva, Siguara B. L.
dc.contributor.authorThomas, Olivier P.
dc.contributor.authorCabezas-Sainz, Pablo
dc.contributor.authorSánchez, Laura
dc.contributor.authorLópez, Rafael
dc.contributor.authorBotana, Luis M.
dc.date.accessioned2018-09-20T16:23:08Z
dc.date.available2018-09-20T16:23:08Z
dc.date.issued2016-11-04
dc.identifier.citationRoel, María; Rubiolo, Juan A. Guerra-Varela, Jorge; Silva, Siguara B. L.; Thomas, Olivier P.; Cabezas-Sainz, Pablo; Sánchez, Laura; López, Rafael; Botana, Luis M. (2016). Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model. Oncotarget 7 (50), 83071-83087
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10379/13691
dc.description.abstractThe marine environment constitutes an extraordinary resource for the discovery of new therapeutic agents. In the present manuscript we studied the effect of 3 different sponge derived guanidine alkaloids, crambescidine -816,-830, and-800. We show that these compounds strongly inhibit tumor cell proliferation by downregulating cyclin-dependent kinases 2/6 and cyclins D/A expression while upregulating the cell cyclin-dependent kinase inhibitors-2A, -2D and -1A. We also show that these guanidine compounds disrupt tumor cell adhesion and cytoskeletal integrity promoting the activation of the intrinsic apoptotic signaling, resulting in loss of mitochondrial membrane potential and concomitant caspase-3 cleavage and activation. The crambescidin 816 anti-tumor effect was fnally assayed in a zebrafish xenotransplantation model confirming its potent antitumor activity against colorectal carcinoma in vivo. Considering these results crambescidins could represent promising natural anticancer agents and therapeutic tools.
dc.publisherImpact Journals, LLC
dc.relation.ispartofOncotarget
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectcrambescidins
dc.subjectcell cycle inhibition
dc.subjectapoptosis
dc.subjectzebrafish xenograft model
dc.subjectcancer treatment
dc.subjectsponge crambe-crambe
dc.subjectcyclin-dependent kinases
dc.subjectp53-mediated g(1) arrest
dc.subjecthuman cancer
dc.subjectcytoskeleton
dc.subjectcells
dc.subjectmitochondria
dc.subjectprogression
dc.subjectanoikis
dc.subjectpathway
dc.titleMarine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model
dc.typeArticle
dc.identifier.doi10.18632/oncotarget.13068
dc.local.publishedsourcehttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=13068&path%5B%5D=41407
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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