RT Journal Article T1 Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model A1 Roel Sánchez, María A1 Rubiolo Gaytán, Juan Andrés A1 Guerra Varela, Jorge A1 Silva, Siguara B. L. A1 Thomas, Olivier P. A1 Cabezas Sáinz, Pablo A1 Sánchez Piñón, Laura A1 López López, Rafael A1 Botana López, Luis Miguel AB The 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 down-regulating cyclin-dependent kinases 2/6 and cyclins D/A expression while up-regulating 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 PB Impact Journals SN 1949-2553 YR 2016 FD 2016 LK http://hdl.handle.net/10347/26114 UL http://hdl.handle.net/10347/26114 LA eng NO Roel M., Rubiolo J. A., Guerra-Varela J., Silva S. B. L., Thomas O. P., Cabezas-Sainz P., Sánchez L., López R., Botana L. M. Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model. Oncotarget. 2016; 7: 83071-83087. Retrieved from https://www.oncotarget.com/article/13068/text/ NO The research leading to these results has received funding from the following FEDER cofunded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and Consellería de Cultura, Educación e Ordenación Universitaria, GRC2013-016. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA – Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA. M.R.S. is an I2C predoctoral fellow. From CAPES Foundation, Brazil (scholarship process: BEX 10184-13-9) DS Minerva RD 22 abr 2026