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Marine guanidine alkaloids crambescidins inhibit tumor growth and activate intrinsic apoptotic signaling inducing tumor regression in a colorectal carcinoma zebrafish xenograft model

Roel, María
; 
Rubiolo, Juan A.
; 
Guerra-Varela, Jorge
; 
Silva, Siguara B. L.
; 
Thomas, Olivier P.
; 
Cabezas-Sainz, Pablo
; 
Sánchez, Laura
; 
López, Rafael
; 
Botana, Luis M.
Identifiers
http://hdl.handle.net/10379/13691
 https://doi.org/10.13025/27858
Publication Date
2016-11-04
Keywords
crambescidins, cell cycle inhibition, apoptosis, zebrafish xenograft model, cancer treatment, sponge crambe-crambe, cyclin-dependent kinases, p53-mediated g(1) arrest, human cancer, cytoskeleton, cells, mitochondria, progression, anoikis, pathway
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Article
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Citation
Roel, 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
Abstract
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 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.
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Publisher
Impact Journals, LLC
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)